Protein Science

by Arthur Lesk

Overview

Written primarily for students embarking on an undergraduate bioscience degree, this primer introduces students to the essential topics in protein science clearly and concisely by describing the basic chemical structure of proteins, the factors that stabilize protein structures, protein function, and protein evolution.

It begins by placing proteins in their general context in life. They are synthesized as amino-acid sequences encoded in genomes, and fold spontaneously to three-dimensional structures. This is the point where life makes the tremendous leap from the one-dimensional world of genome and amino-acid sequences, to the three-dimensional world of protein structures - indeed, the world which we inhabit.

Protein Science prepares readers for later more advanced study of the subject, but will also leave readers who do not go on to such advanced study with a satisfying grasp of the essentials of the subject.

Protein Science is supported by online resources and is available for students and institutions to purchase in a variety of formats.

The e-book offers a mobile experience and convenient access along with functionality tools, navigation features and links that offer extra learning support: www.oxfordtextbooks.co.uk/ebooks

The online resources include:

For students:
- Self-test questions
- Animations of protein structures introduced in the text

For registered adopters of the book:
· Figures from the book, available to download

Product Details

ISBN-13:	9780198846451
Publisher:	Oxford University Press
Publication date:	03/07/2022
Series:	Oxford Biology Primers
Pages:	164
Product dimensions:	9.81(w) x 7.55(h) x 0.30(d)

About the Author

Arthur Lesk, Professor of Biochemistry and Molecular Biology, The Pennsylvania State University

Arthur M. Lesk is Professor of Biochemistry and Molecular Biology at The Pennsylvania State University. He is the author of the highly successful Introduction to Bioinformatics, and Introduction to Genomics, both published by Oxford University Press.

Table of Contents

1 Setting the stage 1

1.1 What are proteins, and what are they for? 2

1.2 The Central Dogma 3

1.3 The spontaneous folding of proteins 4

Protein structures in three-dimensions 4

1.4 Proteins and genomics 7

1.5 Proteomics 7

Protein mass spectrometry 8

Two-dimensional gel electrophoresis 8

1.6 Regulation of protein activity 10

1.7 Protein evolution 12

Domain recombination 12

1.8 Protein dysfunction, and disease 13

1.9 Databases and web sites containing information about proteins 15

2 Protein structure 19

2.1 Proteins are formed of polypeptide chains 20

2.2 The sidechains 21

2.3 Protein folding and denaturation 23

What stabilizes native states of proteins? 23

The native structures of proteins are determined by their sequences of amino acids 25

2.4 Cofactors and post-translational modifications 27

2.5 Protein structures and their analysis 28

Secondary structures: α-helices and β-sheets appear in many proteins 29

Conformational angles define protein conformations 31

Primary, secondary, tertiary, and quaternary structures 31

Supersecondary structures 33

A picture gallery 34

Domains 35

Conformational change 37

Intrinsically-disordered proteins (IDP) 39

2.6 Mutations 40

2.7 Protein families 40

2.8 Protein interactions 44

Diseases of protein aggregation 47

3 Isolation and structure determination of proteins 55

3.1 Protein purification 56

Ammonium sulphate precipitation 57

Size-exclusion chromatography 59

Ion-exchange chromatography 60

Affinity chromatography 60

Specific expression of a target protein 60

3.2 Experimental methods of protein structure determination 61

X-ray crystallography 61

Protein structure determination by nuclear magnetic resonance (NMR) spectroscopy 65

Cryo-electron microscopy 66

3.3 Protein structure prediction 69

Critical Assessment of Structure Prediction-CASP 69

Homology modelling 69

A priori structure prediction 70

4 Protein function 77

4.1 Structural proteins 78

4.2 Enzymes 81

How do enzymes speed up reactions? 82

Enzyme kinetics 83

Regulation of enzyme activity 85

4.3 Antibodies 86

Humanized antibodies 88

4.4 Membrane proteins and receptors 90

4.5 Transport proteins 91

Membrane transport 92

Specificity of passage: the potassium channel 92

Cross-membrane transport with or against a concentration gradient: the mitochondrial electron-transport chain and ATP synthase 92

ATP synthase 94

Voltage-gated channels: transmission of the nerve impulse 97

4.6 Signal reception and transduction 99

G-protein-coupled receptors 100

4.7 Classification of protein function 101

The Enzyme Commission 103

The Gene Ontology™ Consortium 105

Prediction of protein function 107

5 Protein evolution 111

5.1 Evolution is exploration 112

5.2 The importance of regulation 114

5.3 How do we measure the evolutionary divergence of proteins? 117

5.4 The relationship between divergence of sequence and structure 120

Changes affecting local regions of the genome 121

The effects of post-transcriptional events 122

Domain reassembly in evolution 123

5.5 Pathways and limits in the divergence of sequence, structure, and function 125

Divergence of function in the enolase superfamily 127

5.6 Protein evolution on the lab bench 129

Directed evolution 129

Computational protein design 134

Glossary 139

Index 145