Showing papers on "Structural biology published in 1995"

Insights into protein folding using physical techniques: studies of lysozyme and alpha-lactalbumin.

Abstract: Understanding the process of protein folding, during which a disordered polypeptide chain is converted into a compact well-defined structure, is one of the major challenges of modern structural biology. In this article we discuss how a combination of physical techniques can provide a structural description of the events which occur during the folding of a protein. First, we discuss how the rapid kinetic events which take place during in vitro folding can be monitored and deciphered in structural terms. Then we consider how more detailed structural descriptions of intermediates may be obtained from NMR studies of stable, partly folded states. Finally, we discuss how these experimental strategies may be extended to relate the findings of in vitro studies to the events occurring during folding In vivo . The approaches will be illustrated using results primarily from our own studies of the c-type lysozymes and the homologous α-lactalbumins. The conclusions from these studies are also related to those from other systems to highlight their unifying features. On the basis of these results we identify some of the determinants of the events in folding and we speculate on the importance of these in driving folding molecules to their native states.

Guidebook to the Small GTPases

Abstract: During the last few years there has been growing interest in the large family of GTPases structurally related to protooncogene product p21 ras. These proteins share structural similarities but are involved in a large spectrum of biological functions. While members of the ras subfamily regulate cell growth, rho proteins are implicated in the control of cytoskeletal organization in mammalian cells or in bud formation in yeast. Members of the ARF/SAR family are postulated to control vasicle budding, whereas Ypt1/Sec4/rab proteins are thought to regulate vesicle targeting and/or fusion. Owing to their functional divergence, the small GTPases have attracted the attention of many investigators in the fields of structural biology, cell biology, cell growth and differentiation and developmental biology. Numerous studies have contributed important data on the biochemical features, the intracellular focalisation, and in some cases, the function of these proteins. This book contains entries on almost 150 GTPases which have been identified so far, and the search has not yet been exhausted. This large repertoire of information is gathered together in an easy to consult format. This book is intended for research workers in the fields of cell biology, molecular biology, biochemistry, and cancer biology.

NMR in structural biology: a collection of papers by Kurt Wuthrich

Abstract: NMR and structural biology the avenue to three-dimensional protein structure determination in solution establishing credibility for NMR structures of proteins evolution of NMR structure determination with biological macromolecules 1985-94 selected NMR structure determination conformational equilibria and internal mobility in proteins and in solution hydration of proteins and nucleic acids in solution protein folding.

[20] NMR and nucleic acid-protein interactions: The Lac repressor-operator system

Abstract: Publisher Summary This chapter discusses the lac repressor-operator system as an example to illustrate the nuclear magnetic resonance (NMR) approach to protein-DNA recognition. The recognition of DNA sequences, by proteins, lies at the heart of many cellular processes, such as gene regulation, replication and DNA repair. Therefore, the mechanism of protein-DNA interaction constitutes a major problem in molecular biology. Approaches to this problem range from biochemical and genetic studies (mutagenesis of DNA-binding proteins) to the application of the methods of structural biology (X-ray crystallography and NMR spectroscopy). NMR spectroscopy started to contribute around 1985, with the structure elucidation of the lac repressor headpiece and a low-resolution structure of the headpiece-operator complex in 1987, whereas in the first structures all contained a helix-turn-helix motif as the essential DNA-binding sub domain, later a plethora of DNA-binding motifs were characterized, including zinc-fingers, leucine zippers, helix-loop-helix proteins, and even B-sheet DNA-binding proteins. NMR has significantly contributed to this, as often DNA-binding domains of proteins are relatively small, independently folded domains that can be expressed and studied separately. For example, for the various subclasses of zinc-fingers, the first structural information came from NMR. The chapter concludes that the structure of the lac headpiece-operator complex agrees very well with the genetic data, and indeed provides a basis for a detailed interpretation of these data in structural terms.

Structural aspects of the serpin reaction coordinate

Abstract: The important physiological roles and unique folding properties of the 50+ known members of the serpin superfamily have inspired a decade of interest in their structural biology. X-ray crystal structures of reactive-loop cleaved serpins, as well as reactive-loop intact (although inactive) serpins illuminate the inherent plasticity of their β-sheet superstructures, and this plasticity is critical for serpin function. Recent X-ray crystal structures of α1-antichymotrypsin and antithrombin III in their active and partially active forms, respectively, reveal two contrasting serpin conformations which may correlate with native and protease-bound conformations of the serpin reactive loop. In this Perspective, we review the current state of serpin structural biology and highlight the structural inferences on the reaction coordinate of the inhibitory mechanism.