Showing papers in "Annual Review of Biochemistry in 1991"

Proteoglycans: structures and interactions.

Abstract: n, sulfation, L-iduronic acid, glycosam inoglycan-protei n in­ teractions, extracellular matrix.

Model systems for the study of seven-transmembrane-segment receptors.

Abstract: PERSPECTIVES AND SUMMARy 654 SCOPE . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 655 G PROTEIN SIGNALING 655 f3,-AR AND RHODOPSIN SIGNALING: SIMILARITIES AND DIFFERENCES...... 657

Primary Response Genes Induced by Growth Factors and Tumor Promoters

Abstract: AND PERSPECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . 282 IDENTIFICATION OF THE FIRST MITOGEN-INDUCIBLE GENES . . . . . . . . .. . . . . . . . . . 286 THE FOS AND JUN GENE FAMILIES. . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . 287 PRIMARY RESPONSE GENES FROM CELLS TREATED WITH GROWTH FACTORS OR TUMOR PROMOTERS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. .. . . . . . . . . . 290 1. Nuclear Proteins . . . .. . . ......... 291 2. Cytoskeletal and Extracellular Matrix Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 295 3. Transmembrane Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . 295 4. Cytokines ... . . . . . . . . . .. . . . . . . . . . . . . . . . ..... . . .... . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . .. . . .. . . . . . 295 5. Proteins of Unknown Function . . . ... .. .. . .... . . . . . . . . . . . ... . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 297 6. Primary Response Genes from a "Late" Library ... ........ .... 298 REGULATION OF PRIMARY RESPONSE GENE EXPRESSION. ......... . . . .. . . . . . . . . . 299 1. c-fos 299 2. c-jun 303 3. JE . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . 304 4. egr-lIz;if-268/krox24/NGFI-A/TIS8. 304 5. egr-2/ krox20. ..... ... 304 6. NlO/nur77/NGFI-B/TISI ..... . ...... . . . ... . .... ......... . ...... ......... 305 CELL-SPECIFIC RESTRICTION OF PRIMARY RESPONSE GENES . .. . . . . . . . . . . . . . . . . 305 SECONDARY RESPONSE GENES . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. .. . . . . . . . . . 306 DO PRIMARY RESPONSE GENES PLAY CAUSAL ROLES I N MODULATING SECONDARY RESPONSE GENES AND CELLULAR PHySIOLOGy? 306 COMMON PRIMARY RESPONSE GENES AND CELLAND LIGANDSPECIFIC RESPONSES . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . ... . . . . . . . . 307 PRIMARY RESPONSE GENE EXPRESSION IN THE NERVOUS SySTEM 309

Denatured States of Proteins

Abstract: The denatured "state" of a protein is a distribution of many different molecular conformations, the averages of which are measured by experiments. The properties of this ensemble depend sensitively on the solution conditions. There is now considerable evidence that even in strong denaturants such as 6M GuHC1 and 9M urea, some structure may remain in protein chains. Under milder or physiological conditions, the denatured states of most proteins appear to be highly compact with extensive secondary structure. Both theoretical and experimental studies suggest that hydrophobic interactions, chain conformational entropies, and electrostatic forces are dominant in determining this structure. The denaturation reaction of many proteins in GuHC1 or urea can be most simply modelled as a two-state transition between the native structure and a relatively compact denatured state, which then undergoes a gradual increase in radius on further addition of denaturant. However, when a protein acquires a large net charge in acids or bases, it can have two stable denatured populations, one compact and the other more highly unfolded. The prediction and elucidation of the structural details of the non-native states of proteins may ultimately prove to be as difficult as predicting the native structures, particularly for D0, the denatured state under physiological conditions. Just as with the native state, the structure of this biologically important denatured state appears to depend on the amino acid sequence. The development of synthetic, peptide and protein fragment models of the denatured state and the recent progress in NMR spectroscopy provide bases for optimism that new insights will be gained into this poorly understood realm of protein biochemistry.

Lysosomal storage diseases

Abstract: Lysosomal storage diseases (LSDs) are a group of over 70 diseases that are characterized by lysosomal dysfunction, most of which are inherited as autosomal recessive traits. These disorders are individually rare but collectively affect 1 in 5,000 live births. LSDs typically present in infancy and childhood, although adult-onset forms also occur. Most LSDs have a progressive neurodegenerative clinical course, although symptoms in other organ systems are frequent. LSD-associated genes encode different lysosomal proteins, including lysosomal enzymes and lysosomal membrane proteins. The lysosome is the key cellular hub for macromolecule catabolism, recycling and signalling, and defects that impair any of these functions cause the accumulation of undigested or partially digested macromolecules in lysosomes (that is, 'storage') or impair the transport of molecules, which can result in cellular damage. Consequently, the cellular pathogenesis of these diseases is complex and is currently incompletely understood. Several LSDs can be treated with approved, disease-specific therapies that are mostly based on enzyme replacement. However, small-molecule therapies, including substrate reduction and chaperone therapies, have also been developed and are approved for some LSDs, whereas gene therapy and genome editing are at advanced preclinical stages and, for a few disorders, have already progressed to the clinic.

Cell adhesion molecules: implications for a molecular histology

Abstract: PERSPECTIVES AND SUMMARY ... . . ... . . .. . . . .. . . . ..... . . . .. . . . .... . . ... . . ... . 155 CAM TYPES, STRUCTURE, AND BINDING ........ ..... ........ .... . . . ... ..... . . ... . . ..... 1 56 Stru ctu re. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157 B in ding. . . . .. . ... .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 6 1 Transfect ion as a M olecular Histological Tool.. ..... . . ... . . . ... . . ... . . ....... ....... ...... 1 63 CHROMOSOMAL LOCALIZATION, GENE STRUCTURE, AND ALTERNATIVE RNA SPLICING . .. . . . . . . . . . .. . . . . . . . . .... . . 165 EXPRESSION AND SYNTHESIS . . . . .. .. ... . .... . . . . .. . . . . . .. . . ......... . . . . . .. ... 166 B ioc hem ical M odific at ions . . .. ....... . . ... . . . .. . . . .. . . . .. . . . . .. . . ..... ... ..... . . . . . . . . . . . . . . . . . . 167 Signals R egu lating CAM Synth esis In vitro a nd In vivo.. . ... ..... .... . . .... . . . . . . . . . . . . . 168 MORPHOREGULATORY ACTIVITY OF CAMs . . . . .. . . . ... . . .... . . ....... . . . . . . . .. . . . . . . . . . 169 Place-D ep en dent Exp ression and I nt eract ions . . .... .. ... .. .. ..... . . .. . . . . . . . . . . .. . . . . . . . . . . 169 C;oreg ulatill,n with SAM Exp ression .... ..... ......... . .... . . ... . . . .... ... ........ ... 1 7 1 R epu !sln s . . . .. . . . . . . .. . . ... . ... . . . . . . . . . . . . .. . . .. .. . . . ..... .. . . . . . . . . . . . . .. .. . . . .. . .. 1 73 Pertu rb ation of CAM B inding an d Exp ression.. . . ... . . . .. . . . .. . . . . . . .. .. ...... . . . 174 EVOLUTIONARY RELATIONSHIPS 1 75 CAMs IN DISEASE 178 Neuromuscula r an d Neu rol ogical D is orders.. . . . ... . . ... . . . ... .. . ...... . ......... . . . . ... .... 179 Transform ed Cells, Tum ors, an d M etastasis ..... . ........ ...... . . .. . . . ... . . ... . . . . . . . . ..... 1 79 PROSPECTS FOR A MOLECULAR HISTOLOGy 1 8 1

Fidelity mechanisms in DNA replication.

Abstract: BASE INSERTION SELECTIVITY BY DNA POL YMERASES . The Base 1''lSertion Pathway . Structural Aspects to Base Selection by DNA Polymerases . Polymerase Insertion Errors . Fidelity Assays and Major Conclusions . Error Avoidance in Base Insertion----General Conclusions ..... .

Structure and Function of Signal-Transducing GTP-Binding Proteins

Abstract: 1. PERSPECTIVES AND SUMMARy . . . . . . . . . . 350 II . INTRODUCTION. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 1 III. GENERAL CHARACTERISTICS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 354 Tra nslational Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .... . . . . . . . . . . 354 Heterotrimeric G Protein s . . . . . . . . . . ... . . ... . ... . . . .... . . .. . . . . . . . . . . . . . . . . . . . . . . . 356 Ras Protein s . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . ... . . . . . . . . . . .. 357 Structu ral Simi/aritie s Be t ween Vari ou s G TP-Binding Protein s. . . . . . . . . . . . . . . . . 359 IV . MAMMALIAN G PRO TEINS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363 M olecular Entitie s and Gene Organizations of G P rotein s . . . . . . . . . . .... . . . . . . . . . . . ... 363 O verall Stru ctu re of G P rotein a-Su bunits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 368 Structu re -Function Relation s hip of G P rotein a-Subunits . . . . . . . . . . . . . . . ... . . .. . . . .. . . . 368 Structure of fly-Subunits of G Protein . . . . . . . . . . . .. . . . ... ..... . ... . . . . . . ... . . . ... . . . . . . . . 376

The regulation of histone synthesis in the cell cycle

Abstract: AND PERSPECTIVE. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 827 ORGANIZATION OF HISTONE GENES-STRUCTURE OF HISTONE mRNAs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 828 OVERVIEW OF HIS TONE SYNTHESIS IN THE CELL CyCLE . . . . . . . . . . . . . . . . . . . . . . . . 829 TRANSCRIPTIONAL REGULATION . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 832 Higher Eukaryotes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . . ... . . . . . . . . 832 Lower Eukaryotes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..... . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . 841 POSTTRANSCRIPTIONAL REGULATION . . . . . .. . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . .. . . . . . . . .... 847 Higher Eukaryotes. . . . . .. . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ....... . . . . . . . . . . . . . . . .. . . . . . . . 847 Lower Eukaryotes . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...... . . . . . . . . . . . . . . . . . . 853 MULTIPLE FORMS OF REGULATION MODULATE HISTONE mRNA LEVELS IN THE CELL CyCLE . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . . . . . !l55 FUTURE PROSPECTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..... . . .. . . . . . . . . . . . . . . . . . ... .. . . . . .. . . . . . . . . . 856

Signal Transduction Pathways Involving Protein Phosphorylation in Prokaryotes

Abstract: Bacteria are capable of sensing a wide variety of environmental signals, including changes in chemical concentrations, the presence of a host organism, or variation in physical parameters such as temperature, osmolarity, viscosity, or light. One response to changing conditions is to move to a more "favorable" locale; changes in locomotive behavior can be observed less than one second after a change in chemical composition of the medium. Another possible course of action is to adapt the cell to the new environment, either by changing enzyme activity or by altering expression of specific genes or groups of genes. The bacterium may use the modified enzymes or new gene products to adjust to its surroundings temporarily, or to establish a new long-term state (e.g. the sporulation response to starvation).

Ribosomal RNA and Translation

Abstract: BIOCHEMICAL EVIDENCE.. """'''''''' ''''' ''' .... ' " ' ' '' ' Activity of Protein-Depleted RNA . Affinity Labeling and Cross-Linking . . Protection from Chemical and Enzymatic Probes . Binding of IRNA to the A, P, and E Sites . Intermediale States in Translocation: Hybrid Sites . Interactions of Antibiotics with Ribosomal RNA . Elongation Factors and Ribosomal RNA . Initiation Factors and Ribosomal RNA . Subunit Association . RNA-Direcled Biochemical Inactivation .

The enzymology of protein translocation across the Escherichia coli plasma membrane.

Abstract: Converging physiological, genetic, and biochemical studies have established the salient features of preprotein translocation across the plasma membrane of Escherichia coli. Translocation is catalyzed by two proteins, a soluble chaperone and a membrane-bound translocase. SecB, the major chaperone for export, forms a complex with preproteins. Complex formation inhibits side-reactions such as aggregation and misfolding and aids preprotein binding to the membrane surface. Translocase consists of functionally linked peripheral and integral membrane protein domains. SecA protein, the peripheral membrane domain of translocase, is the primary receptor for the SecB/preprotein complex. SecA hydrolyzes ATP, promoting cycles of translocation, preprotein release, Δµ~H+-dependent translocation, and rebinding of the preprotein. The membrane-embedded domain of translocase is the SecY/E protein. It has, as subunits, the SeeY and SecE polypeptides. The SecY/E protein stabilizes and activates SecA and participates in binding it to the membrane. SecA recognizes the leader domain of preproteins, whereas both SecA and SecB recognize the mature domain. Many proteins translocate without requiring SecB, and some proteins do not need translocase to assemble into the plasma membrane. Translocation is usually followed by endoproteolytic cleavage by leader peptidase. The availability of virtually every pure protein and cloned gene involved in the translocation process makes E. coli the premier organism for the study of translocation mechanisms.

Phospholipid transfer proteins.

Abstract: INTROD UCTION AND PERSPECTI VES . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 PHOSPHOLIPID TRANSFER PROTEINS IN MAMMALS, PLANTS , A ND UNICELLULAR ORGANISMS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 Introductory Remarks . . . . . . . ... . . . . . . . . . . . . . . . . " . . . . . . . . .. . . . . . . . .. . " . . .... . .. . . ..... . . . . .. . . 75 Mammalian Tissues . . . . . . . . . . . . . . . . . . ... . . . . . ... . . . . . . . . . . . . . . . . . . . . . . .. . . . . . .. . . . . .. " . . . . . . " . . 75 Plams . ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . 77 yeast. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77 Bacteria. . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . 78 PRIMARY STRUCT URE: LACK OF SEQUEN CE HOMOLOGIES .. . . .. . "..... . . . 79 PROPERTIE S OF T HE LIPID -BINDING S ITE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 ImroduclOry Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . " . . 80 S pe cific Binding Sites for the m·J· and sn-2 Fal y Acyl Chain s . . . . . . . . . . . . . .. . . . . . . . . . 8 1 Use of P holoactivatable Analogs o f pc 82 Spe cifi c Recognition Sites for the Polar He ad Gro ups . . . . . . . . . . . . . . . . . . . . . . . .. .. . . . . . . . . . 83 CARRIERS OF PHOSPHO LIPIDS BETWEEN MEMBRANES . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84 Introductory Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . 84 Mode of Actio n . . . . . . . . . . . .... . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . .. . . . . . . . . . . ..... . . . . . . . . . . . . . . . . . . . 85 Net Transfer versus E xchan ge : Effe ct on Memb ra ne Properties . . . . . . . . . . . . . .. . . . . . . . . . 87 TISS UE D IS TRIBUTION AND INTRACELLULAR LOCA LIZATION . . . . . . . .. . . . . . . . . . 89 Involveme nt of Pero xiso mes .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 STIMULAT ION OF LIPID METABOLISM . . .. .. . . . . . . . . . . . . . . . . . . . . " . . . . . . . . . . . . . . . . . . . . " . . 9 1 Phosphol i pids.. .. ....... " 91 Cholester ol . ...... ... ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . 92 Stero idogenesis . . ... . . . . . . . . . .. . . .. . . . . . . . .... . . . . . .. . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93 ROLE IN MEM BRANE VESICLE FLOW. . . . . . . . . . . . . . . . . .. . . . . . . . . 93 CONCLUDING R EMARK S . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94

Protein-priming of DNA replication

Abstract: PERSPECTIVES AND SUMMARY . ....... . . . . . . . . . . . . ...... ... . . . . ... 40 ADENOVIRUS DNA REPLICATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . . �;;,t���:��� �� �:�:o:::::::::::::::::::::: :::::::::::::::::::::::::::::::::::::::::::: :: :::::::::: Viral Proteins Required for Replication . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . .. . . . . . . . . . Cell�lar Protei�s Required for Replication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Repitcatwn OT/gm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Replication of the Nontemplate Strand . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . BACTERIOPHAGE 4>29 DNA REPLICATION . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . .... ...... . . . . . Replication in Vivo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Replication in Vitro . . . . . . . ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . Viral Proteins Essential for the Initiation of Replication . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . Other Viral Proteins Involved in Replication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Repitcatwn OT/gm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Replication of the Nontemplate Strand . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . BACTERIOPHAGE PRDI DNA REPLICATION ....... . . . . . ....... . . . . . . . .. . . . . . . . ... . .... . . . BACTERIOPHAGE Cp-l DNA REPLICATION . . . . . . . . . . . ...... ..... . . . ...... . . ... . BACTERIOPHAGE HB-3 TP .. . . . . . . . . . . . . . . . . . . . . ........ . . . . . . . . . . . . ....... .. . TERMINAL PROTEINS IN LINEAR PLASMIDS . . . . . . . . . . .... . .. . . . . . . . . . .... . . . . HEPADNAVIRUS TP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . GENOME-LINKED PROTEINS OF RNA VIRUSES . . ....... . CONCLUSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Atrial natriuretic factor and related peptide hormones.

Abstract: I. PERSPECTIVES AND SUMMARY 230 II. CLASSIFICATION OF CARDIAC PEPTIDE HORMONES """"""""""" " "" 231 Type A Natriuretic Peptides . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231 Type B Natriuretic Peptides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233 Type C Natriuretic Peptides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234 III. MOLECULAR BIOLOGY OF ANF GENE EXPRESSION 235 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . " .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235 Factors that Regulate ANF Gene Transcription . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 236 Cis-Acting Sequences. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237 Cardiac Trans-Acting Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 240 IV. PEPTIDE PROCESSING AND RELEASE... ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 242 ANF Processing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 242 ANF Rele·ase.. . . . . . . . . . .. . .. . . . . . . . . . . . . . . . . . ........ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243 V. BIOCHEMISTRY OF PHARMACOLOGIC ACTIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247 ANF Receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247 Physiologic Effects of ANF """"""""""""""""""""""""""""""""" ' " 249

The biochemistry of AIDS.

Abstract: I. HISTORICAL PERSPECTIVES ON HUMAN RETROVIRUSES . . . . . . . . . . . . . . . . . . . . . . . 578 II. BIOLOGICAL PROPERTIES OF HIV . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 580 A. Ta rge t Cell Tropism . .. . .. . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . 580 R. Syncy lia In duction an d Cytopathic E ffect . . . ... . . . . . . .. . . . . . . .. . 58 1 C. Clinical Man ifestations of HIV Infection . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . .. . . . . . . . 582 III. REPLICATION CYCLE OF HIV . . . .. . . . . .... . .. . . . . . .. . . . . . . . .. . . . . . . . . . . . . ... . . . . . . . 583 A. Virus Bin ding , Fusion , an d Entry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 583 B. Synthesis an d Inte gration of P roviral DNA . . . . . .. . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . 586 C. Exp re ssion of Viral Genes . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . .. . . . . . . . 587 D. Assembly an d Release of Matu re Virus . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . .. . . 589 IV. ORGANIZATION AND EXPRESSION OF HIV GENES .. . . . . . . . . . . . . . . . . . . ... . . . . . . . 593 A. The Siru ctu ral Genes. . . ... .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . .... . . .. ... . .. .. .. . . . . . 593 B . The Regulato ry G enes . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . 595 C. The Accessory Genes . . . . . . . . . . . ... . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 599 D. Splicing Pattern . . . .. . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . .. . . . . . . . . . 602 V. NOVEL REGULATORY PATHWAYS IN HIV GENE EXPRESSION . . . . . . . . . . . . . . 604 A . Transcriptional an d Posttransc riptional Activation by Tat / TAR . . . . . . . . . . .. . . . . . . . . . 604 B . Regulation of Splicing/Transport of mRNA by RevlRRE . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . 608 C. Transcriptional Down -Regulation by R ev . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . .. . . . . . . . . . 6 1 0 D. I s N e f a Negative Regulator? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . .. . . . . . . . . . 6 1 1 E. Activation of HIV by Othe r Viruses . .. . .. . . . . . . . . . . . . . .. . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 1 1 VI. IMPACT OF TAT O N CELLULAR FUNCTIONS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . 6 1 2 VII. GENETIC HETEROGENEITy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 1 4 A . Genomic Comple xit y an d Evolution in a Single Infection . . . . . . . . . . . . . . . . . .. . . . . . . . . . 6 1 4 B . Dive rgence of HIV-1 in t he Population . .. . . . . ... . . . . . . . . . . .. . . . . . . . . . . . . . . . . . .. . . . . . . . . . 6 1 6 C. Evo/u tiona ry Divergence of the Human and Simian Immunodeficiency Viru se s . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 1 7 VIII. CURRENT AND FUTURE PROSPECTS FOR AN AIDS VACCINE AND ANTIVIRAL THERAPy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . . 6 1 8

Bacteriophage lambda DNA maturation and packaging.

Abstract: PERSPECTIVES AND SUMMARy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125 HEAD ASSEMBLY: AN OVERVIEW.. . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . 131 Prohead Structure .. . . . . . . . . . .. . . . . . . . . . . . . . . . ... . . . . . . .. . . . . . .. . . .. . . .... . . . . .. . . ..... . . . . . . . . ... 131 DNA Maturation, Packaging, and Head Completion . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131 STRUCTURE AND FUNCTION OF TERMINASE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132 Purification and Properties of the Protomer and of the Small Subunit . . . . . . . . . . . . . . . . 132 Cloning 0./ the Terminase Genes 'and Protein Overproduction . . . . . . ....... ... 132 Functiona.( Domains . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133 STRUCTURE OF COS . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . .. . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 THE FUNCTIONS OF TERMINASE . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . 137 Formation of the Initiation Complex . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . .. . .. . . . . . . 137 Endonucleolytic Activity . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . 142 Prohead Binding . .. .. . . . . . . . . . . . .... .... . . ... . .. . . . . . . . . . .. . . . . . . . . . . . ... . .. . . . . . . . ...... . . . . . ... . 146 DNA Packaging 146 Cutting of the Terminal cos.... . .... . . . . . . . . . . ..... . .. . .. . . . ... . . . . ... 149 CONCLUSIONS. . .. . . . .. . . . . . . . . . ......... ..... . . ..... . ..... . .. ... . .. ...... . ....... .. . . . . . . . .... ...... 150

50 years of biological research--from oxidative phosphorylation to energy requiring transport regulation.

Abstract: In 1930 adenosine triphosphate appeared in the literature from W. A. Engelhardt's work on avian erythrocytes. This was an early example of oxidative phosphorylation in intact cells, and it required methylene blue and oxygen. Both Belitser and I realized that the use of Warburg manometers for aeration was critical in order to generate oxidative phosphorylation of glucose in tissue preparations. Test tube techniques did not work. In 1956 we were able to describe a human type of diabetes called "galactose diabetes," in which consumption of human or cows' milk provokes mental retardation. Replacement of human or cows' milk products with "vegetable milk" formula in early infancy can prevent retardation. We determined that the disease results from a defect of galactose-one-phosphate uridylyl-transferase, a hereditary enzyme. This type of enzyme defect, if discovered and treated in early infancy, is a benign molecular disease. Regulation of transport systems in mammalian cell cultures are frequently complex energized systems. Perhaps my greatest surprise in this regard was the mere fact that an all-cis "odd" hexose-D-allose turned out to be a highly intense down-regulator of the hexose transport system. Additions of inhibitors of oxidative phosphorylation (such as oligomycin or di-nitrophenol) arrested the allose-mediated down-regulation. We have reason to suspect that the strong down-regulator is a phosphorylated form of D-allose. Thus ends my story about oxidative energized biological phosphorylation systems.