Current Opinion In Structural Biology Research Articles

Membrane proteins: Current Opinion in Structural Biology 1993, 3:499–500

Membrane proteins: Current Opinion in Structural Biology 1993, 3:499–500

Lipid sorting and trafficking in cells: Current Opinion in Structural Biology 1993, 3:495–498

Recent advances in the field of lipid sorting include the report of a cell-free system that exhibits ATP-dependent transport of phosphatidylserine to mitochondria. Other investigations describe co-transport of glycosphinogo-lipids with proteins, intra-Golgi movement of gangliosides and mobilization of cholesterol from lysosomes. In addition, the role of transfer proteins in intracellular lipid movement has again been challenged.

Protein engineering as a tool for understanding electron transfer: Current Opinion in Structural Biology 1993, 3:555–563

The ability to engineer proteins in a specific manner is a powerful tool when applied to the study of biological electron transfer. Mutagenesis, semisynthesis, and site-specific modification have been employed to prepare novel electron-transfer proteins; theoretical and experimental work on these proteins has elucidated the factors that tune active-site redox potentials and spectroscopic features as well as the properties that control electron transfer through polypeptide structures.

Lipid transmembrane asymmetry and flip-flop in biological membranes and in lipid bilayers: Current Opinion in Structural Biology 1993, 3:489–494

During the past year, the body of evidence indicating that specific proteins are involved in the transmembrane redistribution of phospholipids in the membranes of eukaryotic cells has grown; however, no such protein has been unambiguously identified. A comparable effort has been directed towards attempting the unravel the mechanism(s) responsible for phospholipid transmembrane segregation and phospholipid scrambling. The physiological implications of the modulation of lipid asymmetry are beginning to emerge; they comprise control of enzyme activity, surface recognition and shape changes.

De novo protein design: from molten globules to native-like states : Current opinion in structural biology 1993, 3:601–610

Recent advances in the field of de novo protein design are examined. The data are examined with respect to the hypothesis that most designed proteins exhibit characteristics similar to those of molten globules. Continuing efforts to produce novel proteins with the specific interactions that define natural proteins are assessed, and the impact that these efforts have had on our understanding of protein structure, stability, and folding is discussed.

Human antibody engineering: Current Opinion in Structural Biology 1993, 3:564–571

The most recent developments in manipulation and selection of antibody genes indicate that the next generation of antibody-based products, particularly those destined for human therapy, could be created entirely in vitro.

The chemical synthesis of peptidomimetic libraries: Current opinion in structural biology 1993, 3:580–584

Molecular diversity as a source of potential drug candidates has been an area of tremendous growth during the past year. The field has been dominated by investigations featuring diverse peptide libraries, generated by both chemical and biological methods. Yet the many undesirable properties of peptides as drugs, such as poor oral availability and low in vivo stability, have prompted chemists to develop methods for the efficient synthesis of conformationally constrained peptide, biopolymer and non-polymeric compound collections.

Lipid domains in biological membranes: Current Opinion in Structural Biology 1993, 3:475–481

There is increasing appreciation for the heterogeneity that exists in the distribution of lipid and protein components within a biological membrane. This review summarizes recent contributions concerning this concept and highlights some current ideas on the existence, formation and function of lipid domains in membranes.

Integral membrane protein structure: transmembrane α-helices as autonomous folding domains: Current opinion in structural biology 1993, 3: 532–540

The transmembrane region of many integral membrane proteins is made up of a bundle of hydrophobic α-helices. Such a structure could result from a two-stage folding process, during which preformed transmembrane helices with independent stability pack without topological rearrangement. This view was originally prompted by experiments in which fragments of transmembrane regions were separately refolded into lipid bilayers and subsequently brought together to yield a functional protein. Other lines of evidence, including the existence of ‘one-helix’ miniproteins, gene-fusion experiments, helix-driven oligomerization of bitopic proteins, and sequence rearrangements in the course of evolution support this view. Although it forms a useful basis for structural predictions, the limitations of the two-stage folding hypothesis are not clearly defined, and the proportion of integral membrane proteins to which it applies remains uncertain. The papers discussed in the present review illustrate recent progress along these lines.

Inhibitors of protein phosphatase-1 and -2A; two of the major serine/threonine protein phosphatases involved in cellular regulation: Current Opinion in Structural Biology 1993, 3: 934–943

The broad specificity type-1 and type-2A protein phosphatases (PP-1 and PP-2A) have emerged as important enzymes in the regulation of eukaryotic cell function. Over the past few years an ever increasing array of potent inhibitor molecules of the catalytic subunits of PP-1 and -2A (PP-1c and PP-2Ac) have been described. These inhibitors are structurally diverse and found in organisms from prokaryote and protist to multicellular eukaryote. This review will focus on recent advances in understanding the structure and properties of these inhibitors and how they may be involved in regulating PP-1c and PP-2Ac in vivo.

Role of the cyclosporin-A-cyclophilin complex, FK506-FK506-binding protein complex and calcineurin in the inhibition of T-cell signal transduction: Current opinion in structural biology 1993, 3:929–933

Our understanding of immunosupressive drug action and intracellular signalling continues to advance. The structures of new immunophilin-lumunosuppressant drug complexes have been formed by the immunophilin-drug complexes and calcineurin are being made by mutagenesis and by the comparison of various protein isotypes. Since the inhibition of calcineurin by the immunophilin-drug complex has been shown to interfere with nuclear localization of NFAT (nuclear factor for activation of T cells), our understanding of the intracellular signal for immune response has become more detailed.

The immunoglobulin superfamily: Current Opinion in Structural Biology 1993, 3:846–852

The steady flow of fresh data on antibody structure and interactions has continued. Recent results have also extended the scope of the available structural information to cover other members of the immunoglobulin superfamily. This review highlights the new perspectives on the structure and functions of the immunoglobulin fold which have emerged from the latest studies.

Helicases and RNA unwinding in translation: Current opinion in structural biology 1993, 3: 953–959

RNA helicases melt regions of duplex RNA in a process that requires energy derived from the hydrolysis of nucleoside triphosphates. The process of protein synthesis in prokaryotes and eukaryotes involves one proven RNA helicase (elF-4A) and several putative RNA helicases. Of these, one group of helicases is thought to unwind secondary structure in the 5′ non-coding region of mRNAs to facilitate ribosome binding. A second group is implicated in ribosome assembly, in particular in ribosomal RNA maturation.

Myosin subfragment-1: structure and function of a molecular motor: Current opinion in structural biology 1993, 3:944–952

The ability for directed movement is a fundamental process of all living systems. Molecules designed for such purposes are ubiquitous in eukaryotic cells and have been the focus of intense investigations for many years. Highlighted in this report is the three-dimensional structure of the myosin motor domain—the first such motor protein to be examined by single-crystal X-ray diffraction analysis.

Cytokine structural taxonomy and mechanisms of receptor engagement: Current opinion in structural biology 1993, 3:815–827

Seven discrete families of cytokines have been identified by sequence and structural analysis. Within this diverse set of protein folds, the hematopoietic growth factors and tumor necrosis factor-like cytokines display a remarkable degree of variation upon their respective topological frameworks. In addition, prototype X-ray structures of ligand-receptor complexes reveal two different strategies of receptor engagement.

HIV protease-ligand complexes: Current Opinion in Structural Biology 1993, 3: 868–874

HIV-1 protease remains a promising target for the treatment of AIDS, and research continues in many laboratories to exploit a knowledge of the structure of the protease and its interactions with inhibitors in the development of an AIDS therapy. Structures of HIV-1 protease in complex with peptide-based inhibitors continue to be reported, and recently structures have appeared for a number of compounds that are not fundamentally peptidyl in nature, compounds that were identified as inhibitors either by screening methods or by structure-based database searches. Three structures of the closely related HIV-2 protease in complex with peptide-based inhibitors have now also been determined.

Dinitrogen reduction by nitrogenase: if N 2 isn't broken, it can't be fixed : Current opinion in structural biology 1993, 3:921–928

Nitrogenase consists of two component metalloproteins, the iron protein and molybdenum-iron protein, which together catalyze the ATP-dependent reduction of dinitrogen to ammonia during biological nitrogen fixation. With the recent crystal structure determinations of both proteins, a structural framework is now available for interpreting the mechanism of nitrogenase at the molecular level.

Rapid evolution of peptide and protein binding properties in vitro.

A significant bottleneck in protein engineering arises from the problem of identifying particular molecules with new functions from a potentially enormous range of peptide or protein variants. Two areas of emerging technology, phage display and multiple peptide synthesis, provide new means of screening huge libraries in vitro for novel binding properties. This review is also published in Current Opinion in Structural Biology 1992, 2:597-604.

Protein engineering for molecular electronics.

Recombinant DNA technology allows the manipulation of the physical properties of proteins that perform electron transport and photochemical processes. Recent work is reviewed that has a potential impact on the development of molecular electronic devices, within a general framework outlining strategies for device fabrication. This review is also published in Current Opinion in Structural Biology 1992, 2:587-592.

Antibody engineering.

Current research into antibody engineering stresses the design of constructs that have both scientific and medical significance. Highlights of the past year include several successful humanizations of non-human antibodies, in which a human antibody is created that possesses the same binding specificity as the non-human one, and phage display of antibodies. This review is also published in Current Opinion in Structural Biology 1992, 2:593-596.