Showing papers in "Annual Review of Biochemistry in 1994"
TL;DR: The role of Ligand in RECEPTOR TRANSFORMATION and ACTIVATION is studied, as well as the role of serotonin, which plays a role in both transformation and inhibition.
Abstract: INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 451 STEROID RECEPTOR SUPERFAMILY . . . . . . . . . . . . . . ... . . ... . . . . . 453 PROTEIN-DNA INTERACTIONS . . . . . . . . . . . . . . . . .. . . .. . . . . . . . . . 455 ROLE OF RECEPTOR IN GENE ACTIVATION AND SILENCING ......... 459 Gene Activation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 459 Gene Silencing . . .. . . .. . ... . . . . . . . . . . . . .... . . . . . ...... . . 462 SYNERGISM BETWEEN DIFFERENT CIS-ACTING ELEMENTS 465 ROLE OF LIGAND IN RECEPTOR TRANSFORMATION AND ACTIVATION . 466 Role of Ligand .... . ... . .. . .... . ..... . . ... . .. . . ........ . 466 Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 471 FACTORS INFLUENCING RECEPTOR ACTIVITY . . . . . . . . . . . . . . . . . . . . 473 Phosphorylation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 473 Ligand-Independent Activation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 475 Nuclear Transcription Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 476 CHROMATIN STRUCTURE AND RECEPTOR ACTION . . . . . . . . . . . . . . . . 479 SUMMARY AND PERSPECTIVES 480
2,960 citations
2,344 citations
1,447 citations
TL;DR: Using AP Endonucleases as Metalloproteins as TrimMing for Reduction of DEOXYRIBOSE DAMages is suggested.
Abstract: DNA GL YCOSYLASES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 921 Thymine Glycol Glycosylases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 921 ForfTUlmidopyrimidine Glycosylase (Fpg/MutM) . . . . . . . . . . . . .. . . . . . . . 924 MutY: A DNA MisfTUltch Glycosylase for Oxidative DafTUlge . . . . . . . . . . . . . 927 Hypoxanthine-DNA Glycosylase 927 5-Hydroxymethyluracil and 5-Hydroxymethylcytosine DNA Glycosylases . . . . . . 928 UV Endonucleases 929 REPAIR OF DEOXYRIBOSE DAMAGES: AP ENDONUCLEASES AND 3'-TRIMMING . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 931 Exonuclease III of E. coli 931 Eukaryotic AP Endonucleases Related to Exonuclease III . . . . . . . . . . . . . . . 933 E. coli Endonuclease IV 937 S. cerevisiae ApnI Protein 938 AP Endonucleases as Metalloproteins 939
1,437 citations
1,177 citations
TL;DR: This chapter discusses the construction of the Peptide-Binding Site, the binding site for Nonpeptide Antagonists, and the role of phosphorous in the biosynthetic pathway.
Abstract: INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101 RECEPTOR STRUCTURE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102 MOLECULAR MODELLING OF G PROTEIN-COUPLED RECEPTORS . .. ... 1 05 LOCALIZATION OF THE LIGAND·BlNDING DOMAIN . . . . . . . . . . . . . . . . 1 07 THE LIGAND-BINDING DOMAIN OF BIOGENIC AMINE RECEPTORS . . . . . 109 THE LIGAND-BINDING DOMAIN OF PEPTIDE RECEPTORS . . . . . . . . . . . . 1 16 Structure of the Peptide-Binding Site . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116 The Binding Site for Nonpeptide Antagonists . . . . . . . . . . . . . . . . . . . . . . . 120 BIOPHYSICAL ANALYSIS OF G PROTEIN-COUPLED RECEPTORS . . . . . . . 122 THE ACTIVATION OF G PROTEINS BY RECEPTORS . . . . . .... . . .. . .. 125 CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128
1,099 citations
TL;DR: The structure of the determinants of apoptosis, a type of cell death, and the role that individual cells play in this process are studied.
Abstract: BIOCHEMICAL PROPERTIES OF STEROID Sa-REDUCTASE . . . . . . . . . . . . 30 Protein Structure . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . 30 pH Optima . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 Kinetic Constants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 Overexpression and Purification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 Intracellular Turnover and Subcellular Localization . . . . . . . . . . . . . . . . . . 36
1,062 citations
TL;DR: The level of intracellular Ca regulates many cellular processes, including neurotransmitter and hormone secretion, the activity of ion channels and enzymes, cytoskeletal function, cell proliferation, and gene expression.
Abstract: The level of intracellular Ca regulates many cellular processes, including neurotransmitter and hormone secretion, the activity of ion channels and enzymes, cytoskeletal function, cell proliferation, and gene expression. Voltage-sensitive Ca channels are among the most heterogeneous of ion channels. In neurons, Ca channels differ in cellular location, biophysical and pharmacological properties, and modulation. A single neuron generally contains multiple types of Ca channels, and such channels are central to the integration and expression of activity in the nervous system. It is clearly important to understand the functional significance of Ca channel diversity; a major research effort that is under way has made clear that different calcium channel types are all part of a family of multisubunit ion channels.
716 citations
TL;DR: The role of NF-Kl3 and AP-l in T Cell Activation and the role of Calcineurin in Other Cells and Species are discussed.
Abstract: INITIATING THE GENETIC PROGRAM LEADING TO T CELL ACTIVATION 1057 Integration of the Diverse Signals Required for T Cell Activation on the Regulatory Regions of Early Genes ..... .. . .. . .. . . ... . 1057 The NF-AT Transcriptional Complex . . . . . . . . . . . . . . . . . . . . . . . . . . .. 1058 An Association Between JUIl D and Octl Appears to Play an Important Role ill Activating the IL-2 Gene ....... . .... .... ..... . .. . . 1062 The Roles of NF-Kl3 and AP-l in T Cell Activation . . . . . ... . . . .. .. . . . 1063 CALCINEURIN: AN ESSENTIAL SIGNALLING INTERMEDIATE ......... 1064 Calcineurin in Other Cells and Species .. . ...... . .. . 1069 Is Calcineurin a Rate-Limiting Step in T Cell Activation? 1070
650 citations
TL;DR: The author reveals the mechanism of trans-activation by Tat in vivo and in vitro and the role of Cellular Factors that Interact with Tat.
Abstract: THE HIV-l PROMOTER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 718 Distal Enhancer Sequences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 718 T Cell Activation Signals and NF-KlJ .. .. . .. ........ ...... . . . . . 721 The Basal Promoter: Spl, TATA, and the Initiator. . . . . . . . . . . . . . . . . . . 722 Downstream Elements: LBP-l, 1ST, and TAR . . . . . . . . . . . . . .. . . . . . . . 723 TRANSCRIPTION ACTIVATION BY TAT THROUGH TAR ... ...... ... . 724 Domain Structure of Tat .. . ......... . ........ 724 Structure of TAR RNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 727 Recognition of Tat by TAR in vivo and in vitro . . . . . . . . . . . . . . . . . . . . . 730 Binding of Cellular Factors to TAR RNA . . . . . . . . . . . . . . . . . . . . . . . . . 731 Cellular Factors that Interact with Tat 733 Mechanism of Trans-activation by Tat . . . . . . . . . . . . . . . . . . . . . . . . . . . 734
647 citations
TL;DR: The idea that all SSBs bind to ssDNA as does the T4 gene 32 protein must be amended, as the vastly different properties of the Eco SSB-binding modes must be considered in studies of DNA replication, recombination, and repair in vitro.
Abstract: There are now several well-documented SSBs from both prokaryotes and eukaryotes that function in replication, recombination, and repair; however, no "consensus" view of their interactions with ssDNA has emerged. Although these proteins all bind preferentially and with high affinity to ssDNA, their modes of binding to ssDNA in vitro, including whether they bind with cooperativity, often differ dramatically. This point is most clear upon comparing the properties of the phage T4 gene 32 protein and the E. coli SSB protein. Depending on the solution conditions, Eco SSB can bind ssDNA in several different modes, which display quite different properties, including cooperativity. The wide range of interactions with ssDNA observed for Eco SSB is due principally to its tetrameric structure and the fact that each SSB protomer (subunit) can bind ssDNA. This reflects a major difference between Eco SSB and the T4 gene 32 protein, which binds DNA as a monomer and displays "unlimited" positive cooperativity in its binding to ssDNA. The Eco SSB tetramer can bind ssDNA with at least two different types of nearest-neighbor positive cooperativity ("limited" and "unlimited"), as well as negative cooperativity among the subunits within an individual tetramer. In fact, this latter property, which is dependent upon salt concentration and nucleotide base composition, is a major factor influencing whether ssDNA interacts with all four or only two SSB subunits, which in turn determines the type of intertetramer positive cooperativity. Hence, it is clear that the interactions of Eco SSB with ssDNA are quite different from those of T4 gene 32 protein, and the idea that all SSBs bind to ssDNA as does the T4 gene 32 protein must be amended. Although it is not yet known which of the Eco SSB-binding modes is functionally important in vivo, it is possible that some of the modes are used preferentially in different DNA metabolic processes. In any event, the vastly different properties of the Eco SSB-binding modes must be considered in studies of DNA replication, recombination, and repair in vitro. Since eukaryotic mitochondrial SSBs as well as SSBs encoded by prokaryotic conjugative plasmids are highly similar to Eco SSB, these proteins are likely to show similar complexities. However, based on their heterotrimeric subunit composition, the eukaryotic nuclear SSBs (RP-A proteins) are significantly different from either Eco SSB or T4 gene 32 proteins. Further subclassification of these proteins must await more detailed biochemical and biophysical studies.
TL;DR: The retroviral enzymes represent important targets for antiviral therapy and one optimistic hope is that a combination of drugs that target all of them may be maximally effective as therapy for AIDS.
Abstract: We have reviewed the current state of knowledge concerning the three enzymes common to all retroviruses. It is informative to consider them together, since their activities are interrelated. The enzymatic activities of RT and IN depend on processing of polyprotein precursors by PR. Furthermore, RT produces the viral DNA substrate to be acted upon by IN. All three of these retroviral enzymes function as multimers, and it is conceivable that specific polyprotein precursor interactions facilitate the multimerization of all of them. The multimeric structures of the enzymes are, however, quite different. PR is a symmetric homodimer whose subunits contribute to formation of a single active site. RT (of HIV, at least) is an asymmetric heterodimer in which one subunit appears to contribute all of the catalytic activity and the second is catalytically inactive, but structurally important. IN also functions minimally as a dimer for processing and joining. The retroviral enzymes represent important targets for antiviral therapy. Considerable effort continues to be focused on developing PR and RT inhibitors. As more is learned about IN, such efforts can be extended. Since these enzymes are critical at different stages in the retroviral life cycle, one optimistic hope is that a combination of drugs that target all of them may be maximally effective as therapy for AIDS.
TL;DR: The author reveals how the design of the Proton Translocation Scheme changed over time from a one-size-fits-all system to a two-way system based on the needs of the individual Protons and the environment.
Abstract: INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 676 THE PROTONMOTIVE ENZYME COMPLEXES OF RESPIRATION ..... . . . 676 A COMPARISON OF MITOCHONDRIAL AND BACTERIAL RESPIRATORY SYSTEMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 677 PROTON TRANSLOCATION SCHEMES . . . . . . . . . . . . . . . . . . . . . . . . . . 679 Cytochrome bd: Formation of a Proton Gradient by Substrate Protons without a Transmembrane Channel . . . . . . . . . . . . . . . . . . . . . . . . . . 679 Cytochrome bo: Proton Translocation by Substrate Protons Plus a Transmembrane Channel 680 Cytochrome c Oxidase: A Proton Pump . . . . . . . . . . . . . . . . . . . . . . . . . . 681 Cytochrome bCI Complex: Proton Translocation by Substrate Protons . . . . . . . 681
TL;DR: Rab Proteins and the TargettinglFusion Paradigm: The role of PHOSPHORYLATION in control of GTPase FUNCTION and the role of regulatory factors Controlling Rab Function is studied.
Abstract: DYNAMINS; A NEW CLASS OF GTPases INVOLVED IN VESICLE FORMATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . 963 THE RAB FAMILY; THE TARGETTING/FUSION PARADIGM . . ..... . . 965 Diversity . .... ... . ..... .. .. ... . ..... . .. .... .. . .. . .... 965 Structural Organization . .. . . . . . .. . . . .. . . . . . .. . . . ... . . . . .... 966 Regulatory Factors Controlling Rab Function ...... .. .... .. .... .. . . 969 Role of Rab Proteins in the Constitutive Pathway. . . . . . . . . . . . . . . . . . . . 971 Control of the Regulated Secretory Pathway by Rab3 . . . . . . . . . . . . . . . . . 976 Control of the Endocytic Pathway (Rab4, 5, 7, and 9) .. .. .. .. .. . ..... 977 Summary: Rab Proteins and the TargettinglFusion Paradigm . . . .... . .... 979 HETEROTRIMERIC G PROTEINS .... . . ....... ..... .. . .... ... . 980 ROLE OF PHOSPHORYLATION IN CONTROL OF GTPase FUNCTION . .... 982 GTPase CONTROL OF ORGANELLE STRUCTURE .... . . . . .. . . . . . .. . 983
TL;DR: Mutant Alleles of NMTl are Powerful Tools for Examining Regulation of Protein N-Myristoylation.
Abstract: REGULATION OF PROTEIN N-MYRISTOYLATION IN SACCHAROMYCES CEREVISIAE . ... . . . . .. . .. . . . . . . .. . . . . . . ... . . . . . . . . 871 NMTl Is Essential for Vegetative Growth . . . . . . . . . .. . . . .. . ... . . .. 872 The Kinetic Mechanism and Substrate Specificities of Nmtlp . . . . . . . . . . . . . 873 Determining the Minimal Catalytic Domain of Nmtlp . . . . . . . . . . . . . . . . . 882 Mutant Alleles of NMTl Are Powerful Tools for Examining Regulation of Protein N-Myristoylation . . . .. . . . . . .. . . . .. . . . ... . .. 883
TL;DR: The Animal Cell Centrosome and the Spindle Pole Body of Yeast Are Structurally Distinct, but Functionally Similar.
Abstract: THE STRUCTURE OF THE CENTROSOME . . . . . . . . . . . . . . . . . . . . . . . . 641 The Centriole Is a Complicated Structure of Unknown Function .. . . . .. . . . 642 The Centrosome Undergoes Characteristic Structural Changes during the Cell Cycle .. ..... .... ...... ..... ... ..... ... . ... . 643 The Animal Cell Centrosome and the Spindle Pole Body of Yeast Are Structurally Distinct, but Functionally Similar . . . . . . . . . . . . . 643
TL;DR: The role of language and environment in pairing and Strand Exchange is explored in more detail in the chapter on Homologous Pairing andStrand Exchange.
Abstract: PRINCIPLES OF HOMOLOGOUS PAIRING AND DNA STRAND EXCHANGE . Homologous Pairing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . DNA Strand Exchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Energetic Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Experimental Assays . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
TL;DR: Besides the relatively small contribution from commercial ammonical fertilizer production, replenishing of the nitrogen pool falls mainly to a limited number of physiologically diverse microbes that contain the nitrogenase enzyme system.
Abstract: In the simplest terms, the biological nitrogen cycle is the reduction of atmospheric dinitrogen (N2) to ammonia with the subsequent reoxidation ammonia to dinitrogen (1). At the reduction level of ammonia, nitrogen incorporated into precursors for biological macromolecules such as proteins and nucleic acids. Reoxidation of ammonia to dinitrogen ("denitrification") by a variety of microbes (by way of nitrite and other oxidation levels of nitrogen) leads to the depletion of the "fixed," biologically usable, nitrogen pool. Besides the relatively small contribution from commercial ammonical fertilizer production, replenishing of the nitrogen pool falls mainly to a limited number of physiologically diverse microbes (e.g. eubacteria and archaebacteria; free-living and symbiotic; aerobic and anaerobic) that contain the nitrogenase enzyme system.
TL;DR: The search for spatial patterns of Replication Forks within the Nucleus and the Paradox of Eukaryotic Replication Origins are investigated.
Abstract: I. ORIGINS OF REPLICATION . . . . . . . . . . . . . . . .. . . . . . . . . . . . .. . . 746 Origins of Replication in S. cerevisiae . . . . . . . . . . . . . . . . . . . . . . . . . . . 746 Evidence for Specific Initiation in the Chromosomes of Higher Eukaryotes . . . . 748 Are Specific Origin Sequences Required for Replication of Plasmids in Cells of Higher Eukaryotes? . .. . . ... . .. .. . . . . .. . . . .. . .. .. 749 Does Replication Initiate at Random Positions in Early Embryos? . . ... . . . . 752 Resolving the Paradox of Eukaryotic Replication Origins . . . . . . . . . . . . . . . 752 Spatial Patterns of Replication Forks within the Nucleus . . . . . .. . .. . . . .. 753
TL;DR: The C. crescentus Chromosomal Origin of Replication and Cell-Cycle Plasmid Replication in C.crescentus are described.
Abstract: INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 420 PROTEIN LOCALIZATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 421 Chemoreceptor Polar Targeting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 421 Cell Type-Specijic Chemoreceptor Turnover . . . . . . . . . . . . . . . . . . . . . . . 423 ASYMMETRY OF POLAR ORGANELLE BIOGENESIS 424 The Flagellum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 424 The Stalk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . ... . 435 CELL TYPE-SPECIFIC DNA REPLICATION . . . . . . . . . . . . . . . . . . . . . . . 438 Nucleoid Polarization and Chromosome Partitioning . . . . . . . . . . . . . . . . . . 439 The C. crescentus Chromosomal Origin of Replication . . . . . . . . . . . . . . . . 440 Cell-Cycle Plasmid Replication in C. crescentus . . . . . . . . . . . . . . . . . . . . 442 DNA Replication Genes . . . . . . . . . . . . . . . . . . . . . 443 Cell-Cycle Control of DNA Methylation ., . . . . . . . . . . . . . . . . . . . . . . . . 444
TL;DR: The role of the NMDA Receptor and the Metabotropic Glutamate Receptor in the Central Nervous System is studied as well as possible control Mechanisms at Presynaptic Sites and Postsynaptic Sites.
Abstract: WHY IS SYNAPTIC REGULATION IMPORTANT? 571 WHAT WE KNOW AND WHAT WE DON'T KNOW . ... .... '" ... . .. . 572 Classes of Synapses in the Central Nervous System ... . .. . . . ... ... . .. 572 Forms of Usage-Dependent Synaptic Regulation. . . . . . . . . . . . . . . . . . . . . 574 A Biochemist's Introduction to Quantal Analysis " , 575 Differences Between the Neuromuscular Junction (the Traditional Model) and CNS Synapses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 576 LONG-TERM POTENTIATION AT HIPPOCAMPAL SYNAPSES. . . . . . . . . . . 578 Associative and Non-Associative LTP . .. .. . ... .. ..... ... ..... . . . 578 Role of the NMDA Receptor .. . ... . .. . _ .. . lRoleoftheNMDAReceptor 579 Postsynaptic Calcium . .. . . . .. ... . . .... . ... . .... . . . . ....... 580 Role of the Metabotropic Glutamate Receptor . . . . . . . . . . . . . . . . . . . . . . 582 BIOCHEMICAL ISSUES AND OPPORTUNITIES . . . . . . . . . . . . . . . . . . . . . 582 A Retrograde Messenger . .. . .. ... .. . ... . . . . . . .. . .. . .. ..... . 582 Possible Control Mechanisms at Presynaptic Sites . . .. . .... . .. . .. . .. . 587 Possible Control Mechanisms at Postsynaptic Sites . . . . . . . . . . . . . . . . . . . 590 DIRECTIONS FOR THE FUTURE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 595