抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Throughout the biological world, a 30 A hydrophobic film typically delimits the environments that serve as the margin between life and death for individual cells. Biochemical and biophysical findings have provided a detailed model of the composition and structure of membranes, which includes levels of dynamic organization both across the lipid bilayer (lipid asymmetry) and in the lateral dimension (lipid domains) of membranes. How do cells apply anabolic and catabolic enzymes, translocases and transporters, plus the intrinsic physical phase behaviour of lipids and their interactions with membrane proteins, to create the unique compositions and multiple functionalities of their individual membranes?

/pdf/membrane-lipids-where-they-are-and-how-they-behave-1rycz1l7v8.pdf

Membrane lipids: where they are and how they behave.

The parasite Plasmodium falciparum is responsible for hundreds of millions of cases of malaria, and kills more than one million African children annually. Here we report an analysis of the genome sequence of P. falciparum clone 3D7. The 23-megabase nuclear genome consists of 14 chromosomes, encodes about 5,300 genes, and is the most (A + T)-rich genome sequenced to date. Genes involved in antigenic variation are concentrated in the subtelomeric regions of the chromosomes. Compared to the genomes of free-living eukaryotic microbes, the genome of this intracellular parasite encodes fewer enzymes and transporters, but a large proportion of genes are devoted to immune evasion and host-parasite interactions. Many nuclear-encoded proteins are targeted to the apicoplast, an organelle involved in fatty-acid and isoprenoid metabolism. The genome sequence provides the foundation for future studies of this organism, and is being exploited in the search for new drugs and vaccines to fight malaria.

/pdf/genome-sequence-of-the-human-malaria-parasite-plasmodium-1d9r2ld5m6.pdf

Genome sequence of the human malaria parasite Plasmodium falciparum

Infrared spectroscopy of proteins.

Denitrification is a distinct means of energy conservation, making use of N oxides as terminal electron acceptors for cellular bioenergetics under anaerobic, microaerophilic, and occasionally aerobic conditions. The process is an essential branch of the global N cycle, reversing dinitrogen fixation, and is associated with chemolithotrophic, phototrophic, diazotrophic, or organotrophic metabolism but generally not with obligately anaerobic life. Discovered more than a century ago and believed to be exclusively a bacterial trait, denitrification has now been found in halophilic and hyperthermophilic archaea and in the mitochondria of fungi, raising evolutionarily intriguing vistas. Important advances in the biochemical characterization of denitrification and the underlying genetics have been achieved with Pseudomonas stutzeri, Pseudomonas aeruginosa, Paracoccus denitrificans, Ralstonia eutropha, and Rhodobacter sphaeroides. Pseudomonads represent one of the largest assemblies of the denitrifying bacteria within a single genus, favoring their use as model organisms. Around 50 genes are required within a single bacterium to encode the core structures of the denitrification apparatus. Much of the denitrification process of gram-negative bacteria has been found confined to the periplasm, whereas the topology and enzymology of the gram-positive bacteria are less well established. The activation and enzymatic transformation of N oxides is based on the redox chemistry of Fe, Cu, and Mo. Biochemical breakthroughs have included the X-ray structures of the two types of respiratory nitrite reductases and the isolation of the novel enzymes nitric oxide reductase and nitrous oxide reductase, as well as their structural characterization by indirect spectroscopic means. This revealed unexpected relationships among denitrification enzymes and respiratory oxygen reductases. Denitrification is intimately related to fundamental cellular processes that include primary and secondary transport, protein translocation, cytochrome c biogenesis, anaerobic gene regulation, metalloprotein assembly, and the biosynthesis of the cofactors molybdopterin and heme D1. An important class of regulators for the anaerobic expression of the denitrification apparatus are transcription factors of the greater FNR family. Nitrate and nitric oxide, in addition to being respiratory substrates, have been identified as signaling molecules for the induction of distinct N oxide-metabolizing enzymes.

/pdf/cell-biology-and-molecular-basis-of-denitrification-red4l5iffz.pdf

Cell biology and molecular basis of denitrification.

New textbooks at all levels of chemistry appear with great regularity. Some fields like basic biochemistry, organic reaction mechanisms, and chemical thermody namics are well represented by many excellent texts, and new or revised editions are published sufficiently often to keep up with progress in research. However, some areas of chemistry, especially many of those taught at the graduate level, suffer from a real lack of up-to-date textbooks. The most serious needs occur in fields that are rapidly changing. Textbooks in these subjects usually have to be written by scientists actually involved in the research which is advancing the field. It is not often easy to persuade such individuals to set time aside to help spread the knowledge they have accumulated. Our goal, in this series, is to pinpoint areas of chemistry where recent progress has outpaced what is covered in any available textbooks, and then seek out and persuade experts in these fields to produce relatively concise but instructive introductions to their fields. These should serve the needs of one semester or one quarter graduate courses in chemistry and biochemistry. In some cases, the availability of texts in active research areas should help stimulate the creation of new courses."

Biomembranes: Molecular Structure and Function

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

Energy Transduction by Cytochrome Complexes in Mitochondrial and Bacterial Respiration: The Enzymology of Coupling Electron Transfer Reactions to Transmembrane Proton Translocation

The cytochrome bd respiratory oxygen reductases

It has been estimated that about 90% of the reduction of molecular oxygen in the biosphere is catalyzed by respiratory oxidases (95). Much of this is accomplished by a wide variety of bacterial oxidases. It has long been recognized that bacterial respiratory systems are branched, having a number of distinct terminal oxidases, rather than the single cytochrome c oxidase present in most eukaryotic mitochondrial systems. This multiplicity of oxidases in bacteria has long been a source of confusion, both in terms of the nature of the enzymes themselves and in terms of the rationale for such complex systems. During the past several years, it has been recognized that most of the bacterial oxidases, despite differences in their substrates (quinol versus cytochrome c), oxygen affinities, and heme types and metal compositions, are closely related members of a single superfamily called the heme-copper oxidase superfamily. A large number of enzymes which just a few years ago were considered to be totally unrelated are now known to be close relatives. This recognition has provided considerable order to a chaotic field, and the research that has been stimulated in this field has generated new insights into heme biosynthesis and the evolution of respiratory systems. The heme-copper oxidase superfamily also includes the eukaryotic mitochondrial oxidases. Much of the impetus for pursuing the study of the bacterial oxidases has been to exploit the experimental advantages offered by the prokaryotic systems to learn about the structures and the functional mechanisms common to the members of the superfamily. The mitochondrial cytochrome c oxidase (primarily the bovine oxidase) has long been the object of intensive study (for reviews, see references 6, 10, 17, 20, 42, 59, and 86). This enzyme catalyzes the four-electron reduction of molecular oxygen to two molecules of water and utilizes the free energy available from this reaction to pump protons (one per electron) across the mitochondrial inner membrane, thus generating a transmembrane proton electrochemical gradient, or proton motive force (118). Although they typically contain only 3 or 4 subunits, in contrast to the 13-subunit mammalian enzyme, the bacterial oxidases catalyze the reduction of dioxygen and pump protons as efficiently as the mitochondrial oxidases do (39). Studies of several of the bacterial oxidases have made a very significant contribution to our knowledge of

The superfamily of heme-copper respiratory oxidases.

Proton translocation coupled to oxidation of ubiquinol by O{sub 2} was studied in spheroplasts of two mutant strains of Escherichia coli, one of which expresses cytochrome d, but not cytochrome bo, and the other expressing only the latter. O{sub 2} pulse experiments revealed that cytochrome d catalyzes separation of the protons and electrons of ubiquinol oxidation but is not a proton pump. In contrast, cytochrome bo functions as a proton pump in addition to separating the charges of quinol oxidation. E. coli membranes and isolated cytochrome bo lack the Cu{sub A} center typical of cytochrome c oxidase, and the isolated enzyme contains only 1Cu/2Fe. Optical spectra indicate that high-spin heme o contributes < 10% to the reduced minus oxidized 560-nm band of the enzyme. Pyridine hemochrome spectra suggest that the hemes of cytochrome bo are not protohemes. Proteoliposomes with cytochrome bo exhibited good respiratory control, but H{sup +}/e{sup {minus}} during quinol oxidation was only 0.3-0.7. This was attributed to an inside out orientation of a significant fraction of the enzyme. Possible metabolic benefits of expressing both cytochromes bo and d in E. coli are discussed.

Robert B. Gennis

Papers

Biomembranes: Molecular Structure and Function

Energy Transduction by Cytochrome Complexes in Mitochondrial and Bacterial Respiration: The Enzymology of Coupling Electron Transfer Reactions to Transmembrane Proton Translocation

The cytochrome bd respiratory oxygen reductases

The superfamily of heme-copper respiratory oxidases.

Properties of the two terminal oxidases of Escherichia coli.