Fibrous Proteins: Amyloids, Prions and Beta Proteins (eBook)

Andrey Kajava, David A.D. Parry, John M. Squire (Autoren)

eBook Download: PDF

2006 | 1. Auflage
328 Seiten
Elsevier Science (Verlag)
978-0-08-046895-2 (ISBN)

Infos

Amyloids, Prions and Beta Proteins is the last volume of the three-part thematic series on Fibrous Proteins in the Advances in Protein Chemistry serial. Fibrous proteins act as molecular scaffolds in cells providing the supporting structures of our skeletons, bones, tendons, cartilage, and skin. They define the mechanical properties of our internal hollow organs such as the intestines, heart, and blood vessels. This volume covers such topics as Beta-Structures in Fibrous Proteins, B-Silks: Enhancing and Controlling Aggregation, Beta-Rolls, Beta-Helices and Other Beta-Solenoid Proteins, Natural Triple B-Stranded Fibrous Folds, Structure, Function and Amyloidogenesis of Fungal Prions: Filament Polymorphism and Prion Variants, X-Ray Fiber and powder Diffraction of PRP Prion Peptides, From the Polymorphism of Amyloid Fibrils to Their Assembly Mechanism and Cytotoxicity, Structural Models of Amyloid-like Fibrils.

Inhalt

Front Cover 1
Fibrous Proteins: Amyloids, Prions and Beta Proteins 3
Copyright Page 4
Contents 6
Chapter 1: beta-Structures in Fibrous Proteins 9
Abstract 9
I. Introduction 9
II. Characteristics of Simple beta-Structures 12
III. Diversity of beta-Structural Fibrous Folds Revealed by Crystallographic Studies 15
IV. Recent Advances in Structural Studies of Amyloid and Prion Fibrils 18
V. Conclusions 20
References 21
Chapter 2: beta-Silks: Enhancing and Controlling Aggregation 25
Abstract 25
I. Introduction 26
II. beta-Silk: An Optimized System for Controlled Assembly and Aggregation 30
III. Role and Function of beta-Sheet Assembly in Silk Proteins 38
IV. Fibril Assembly: Amyloid Nature of Silk? 47
V. Conclusions 49
Acknowledgments 50
References 50
Chapter 3: beta-Rolls, beta-Helices, and Other beta-Solenoid Proteins 63
Abstract 64
I. Introduction 64
II. Diversity and Classification of beta-Solenoids 69
III. Capping and Bulging 78
IV. Multistranded beta-Solenoids 79
V. Relationship Between beta-Solenoid Structures and Their Amino Acid Sequences 82
VI. Relationship Between beta-Solenoid Structures and Their Functions 93
VII. Evolution of beta-Solenoid Proteins 95
VIII. Perspective 97
Acknowledgment 98
References 98
Chapter 4: Natural Triple beta-Stranded Fibrous Folds 105
Abstract 105
I. Introduction 106
II. Crystal Structures of Viral Fibers 107
III. Stability, Folding, and Assembly of Fibrous Proteins 119
IV. Future Research Directions 124
References 126
Chapter 5: Structure, Function, and Amyloidogenesis of Fungal Prions: Filament Polymorphism and Prion Variants 133
Abstract 134
I. Introduction 135
II. Prion Domains and Functional Domains 143
III. Filament Formation In Vivo and In Vitro 145
IV. Filament Formation and Prion Conversion Are Based on Amyloidosis of the Prion Domains 151
V. Experimentally Derived Constraints on Prion Filament Structure 159
VI. Structural Models for Prion Amyloid Filaments 165
VII. Other Structural Considerations 170
VIII. Prion Variants 174
IX. Perspective 179
Acknowledgments 180
References 180
Chapter 6: X-Ray Fiber and Powder Diffraction of PrP Prion Peptides 189
Abstract 189
I. Introduction 190
II. Prion Hypothesis 194
III. Sequence Analysis 197
IV. Prion Alanine-Rich Domain 199
V. Amyloidogenic Core Domains 206
VI. Polyalanine 207
VII. Polyglutamine 211
VIII. Conclusions 213
Acknowledgments 214
References 214
Chapter 7: From the Polymorphism of Amyloid Fibrils to their Assembly Mechanism and Cytotoxicity 225
Abstract 225
I. Introduction 225
II. Polymorphism of Amyloid Fibrils 227
III. Soluble Forms of Amyloid Peptides 231
IV. Depicting Intermediate Stages of Amyloid Fibril Assembly 231
V. What Is the Mechanism of Small Oligomer-Induced Cytotoxicity? 234
VI. Conclusions 237
Acknowledgments 237
References 237
Chapter 8: Structural Models of Amyloid-Like Fibrils 243
Abstract 243
I. Introduction 244
II. Refolding Models 247
III. Gain-of-Interaction Models 251
IV. Models of Natively Disordered Proteins 265
V. Fibril Properties and Their Relation to Structural Models 272
VI. Conclusions 279
References 280
Author Index 291
Subject Index 317

Textauszug

β‐Structures in Fibrous Proteins

Andrey V. Kajava*, John M. Squire†, David A.D. Parry‡    * Centre de Recherches de Biochimie Macromoléculaire, CNRS FRE‐2593, 1919 Route de Mende, 34293 Montpellier Cedex 5, France
† Biological Structure and Function Section, Biomedical Sciences Division, Imperial College London, London SW7 2AZ, United Kingdom
‡ Institute of Fundamental Sciences, Massey University, Palmerston North, New Zealand

Abstract

The β‐form of protein folding, one of the earliest protein structures to be defined, was originally observed in studies of silks. It was then seen in early studies of synthetic polypeptides and, of course, is now known to be present in a variety of guises as an essential component of globular protein structures. However, in the last decade or so it has become clear that the β‐conformation of chains is present not only in many of the amyloid structures associated with, for example, Alzheimer's Disease, but also in the prion structures associated with the spongiform encephalopathies. Furthermore, X‐ray crystallography studies have revealed the high incidence of the β‐fibrous proteins among virulence factors of pathogenic bacteria and viruses. Here we describe the basic forms of the β‐fold, summarize the many different new forms of β‐structural fibrous arrangements that have been discovered, and review advances in structural studies of amyloid and prion fibrils. These and other issues are described in detail in later chapters.

I Introduction

Elucidation of the three‐dimensional structures of β‐structural fibrous proteins has attracted the interest of scientists for more than 50 years. In the early days, the objects of these studies were predominantly the naturally occurring fibrous assemblies obtained from β‐silk and stretched mammalian β‐keratin (Astbury and Street, 1931), but the crystalline structures formed by some synthetic polypeptides (Fraser and MacRae, 1973) were also investigated in detail. An important outcome of these studies was a description of the two basic β‐structural arrangements found in proteins: the parallel and antiparallel pleated β‐sheet structures (Fraser et al., 1969; Pauling and Corey, 1951; Fig. 1A and B). Most of these β‐sheet structures are nonplanar (i.e., twisted), as shown initially by Fraser et al. (1971) for feather keratin, but subsequently seen widely in virtually all crystalline globular proteins (Salemme and Weatherford, 1981). At the same time, significant progress was achieved in establishing the orientation of the β‐crystallites that composed the pleated sheet structures in β‐silk, β‐keratin, and the other fibrous polypeptide structures (Bradbury et al., 1960; Fraser and MacRae, 1973). More recently, research on fibrous β‐proteins has been stimulated by the observation that amyloids, prion fibrils, and a variety of denaturated globular proteins have cross‐β structures (Fig. 1C and D), in which the polypeptide chains are oriented perpendicular to the plane of the fibrils axis (Blake and Serpell, 1996; Caughey et al., 1991; Eanes and Glenner, 1968; Kirschner et al., 1986). The incidence of amyloid fibrils in important human diseases has attracted considerable efforts to solve their structures at the atomic level. Despite this, however, the structure of the amyloid fibril, and in particular the lateral packing of the β‐strands and their orientation (parallel vs antiparallel) within the β‐sheets, remains unknown. This failure may be attributed in part to the fact that methods of determining high‐resolution structure (protein crystallography and NMR spectroscopy) cannot be used because of the polymeric character and insolubility of the fibrils involved. Accordingly, X‐ray fiber diffraction, electron microscopy (EM), optical spectroscopy, and other biophysical approaches have been the principal sources of data underlying the models of β‐structural fibrils presented to date.

Fig. 1 The basic arrangements of β‐strands in hydrogen‐bonded β‐sheets (A) parallel chains, (B) antiparallel chains. Green spheres of different sizes denote side chain groups directed either toward (large spheres) or away from (small spheres) from the reader. Hydrogen bonds are shown by red dotted lines. Other colors follow the standard CPK scheme. (C) Chain folding back onto itself in a cross‐β sheet. (D) Stacking of several sheets as in (C); the spacing of the stacks, shown as 11 Å, is actually very variable depending on the nature of the R groups.

Over the last 13 years, there have been major advances in the study of fibrous β‐proteins. In particular, this period has been marked by a rapid emergence of new structural information. First, a number of crystal structures having elongated β‐structural fibrous topologies have been resolved by X‐ray crystallography, thanks to improved expression and crystallization strategies. Second, several new experimental techniques, including solid‐state NMR, scanning transmission EM mass measurements, and electron paramagnetic resonance spectroscopy of spin‐labeled derivatives, have been applied successfully and these have provided significant constraints on the structural models for β‐silk, amyloid, and prion fibrils. One of the aims in preparing this book has been to provide an overview of the progress made in the elucidation of the β‐fibrous proteins over the past decade.

II Characteristics of Simple β‐Structures

To set the scene for the detailed chapters in the rest of the book, we describe here the main features of the simple β‐structural components of proteins. The parallel and antiparallel β‐structures in Fig. 1A and B show certain characteristic features. There is a repeat along the chain direction (vertical in Fig. 1A and B) which consists of two‐amino acid residues and is often about 6.5‐ to 7‐Å long. The β‐sheet is not planar but pleated to permit the side chains (R groups) of the amino acids to project out from the plane of the backbone‐pleated sheet. In Fig. 1A and B, the backbone‐pleated sheets are in the plane of the page and the R groups are imagined projecting above and below this plane. The other relatively constant dimension in β‐structures is the repeat distance in the direction of the hydrogen bonding between adjacent chains. In the antiparallel β‐structures this distance is about 9.6 Å, but this contains two chains so there is a marked repeat at half of this, about 4.8 Å. In the silks (Dicko et al., this volume) and in stretched keratin, the chain axis is normally parallel to the fiber axis direction, as envisaged in Fig. 1A and B for a “vertical” fiber axis. However, early studies of synthetic polypeptides (Bradbury et al., 1960) showed that some structures existed where the chain axis was perpendicular to the direction of stroking or stretching when the polypeptide solutions were oriented before drying. This was termed the cross‐β structure (Fig. 1C); it was also found to exist in a number of denatured globular and fibrous proteins (see summary in Fraser and MacRae, 1973). The term “cross‐β structure” was originally used to imply an antiparallel arrangement of β‐strands lying perpendicular to the fibril axis. It is now used more generally, however, to describe any chain arrangement of β‐strands (parallel, antiparallel, or mixed) with a chain orientation perpendicular to the fibril axis. The in‐plane spacings in cross‐β structures are much the same as in Fig. 1A and B, except that the hydrogen‐bonded direction (9.6‐ and 4.8‐Å repeats) is now along the fiber axis and the in‐chain repeat of 7 Å is perpendicular to the fiber axis.

For β‐crystallites in general (i.e., for those structural elements in which the chain directions lie either in a similar direction to the fibril axis or which lie approximately perpendicular to it), the repeat in the third dimension has proved to be quite variable. The hydrogen‐bonded sheets depicted in Fig. 1A–C can sometimes stack together as shown in Fig. 1D for a cross‐β antiparallel sheet. The exact separation of the sheets is much more variable than the other repeats and depends crucially on the nature of the side chains (R...

Produkt-Details

• Erscheint lt. Verlag: 12.12.2006
• Sprache: englisch
• Themenwelt: Sachbuch/Ratgeber
• Themenwelt: Studium ► 1. Studienabschnitt (Vorklinik) ► Physiologie
• Themenwelt: Naturwissenschaften ► Biologie ► Biochemie
• Themenwelt: Naturwissenschaften ► Biologie ► Genetik / Molekularbiologie
• Themenwelt: Technik
• ISBN-10: 0-08-046895-0 / 0080468950
• ISBN-13: 978-0-08-046895-2 / 9780080468952