Introduction to Protein Science Architecture, Function, and Genomics

by Lesk, Arthur M.

• ISBN13: 9780199265114
• ISBN10: 0199265119
• Edition: 1st
• Format: Paperback
• Copyright: 2004-04-15
• Publisher: Oxford University Press

Summary

Proteins are essential to life, having a vital role in all living organisms. They are the ultimate micro machines: some are building blocks, joining with other substances to make the cells from which we are all formed. Some are catalysts, speeding up essential biochemical reactions to keep ourcells alive. Yet others help cells to communicate, to move, and to build up the complex mix of tissues that make up our bodies. Introduction to Protein Science provides a broad ranging introduction to the contemporary study of proteins suitable for students on biosciences degrees internationally. Starting by describing the structure of proteins and how these structures can be studied, the book goes on to illustrate thewide range of functions that proteins have, showing how the shape of a protein is intimately linked to the function that it has. The book then describes how new experimental and computational techniques are helping us to predict a protein s structure and function, and how this is paving the way forus to design new proteins with specific characteristics, with exciting implications in areas such as drug design. Written by Arthur Lesk, the author of the highly successful Introduction to Bioinformatics, this book offers the same clear, student friendly approach to an equally important area of bioscience. Recent advances in genomics and proteomics have paved the way for an explosion of interest in proteinstructure and function. This book captures the current state of excitement in a way that all biosciences students will find appealing. Online Resource Centre: - Downloadable figures - A Web link library - Animated illustrations (pictures of complicated structures are much more effective if presented as animations; this will take the form of a computer-readable supplement to the book). All these will be available on the Online Resource Centre at www.oup.com/uk/booksites/biosciences/

Author Biography

Dr. Arthur Lesk is a Senior Research Associate, Department of Haematology, University of Cambridge.

Table of Contents

Preface	xiii
The Ribosome---the Fulcrum of Genomics	1	(12)
Introduction	1	(4)
Structural studies of ribsomes by X-ray crystallography and electron microscopy	3	(2)
The genetic code	5	(2)
The biological context of protein synthesis---the basis of evolution	7	(4)
Regulation	9	(1)
Useful Web Sites	10	(1)
Recommended Reading	10	(1)
Exercises, Problem, and Weblem	11	(2)
Genomics and Proteomics	13	(60)
Genome sequences	14	(1)
Gene sequences determine amino acid sequences	15	(4)
Amino acid sequences determine protein structures	19	(5)
Secondary structure	21	(1)
Tertiary and quaternary structure	22	(1)
Protein stability and denaturation	22	(2)
A survey of protein structures and functions	24	(15)
Fibrous proteins	25	(3)
Enzymes---proteins that catalyse chemical reactions	28	(3)
Antibodies	31	(1)
Inhibitors	31	(1)
Carrier proteins	32	(1)
Membrane proteins	32	(3)
Receptors	35	(1)
Regulatory proteins	36	(3)
Motor proteins	39	(1)
Protein folding patterns	39	(5)
Folding patterns in native proteins---themes and variations	43	(1)
Modular structure of proteins	44	(2)
Protein evolution	46	(2)
How do proteins develop new functions?	48	(1)
Integration and control of protein function	48	(4)
Protein expression patterns in space and time: proteomics	52	(10)
Subcellular localization	52	(1)
Protein turnover	53	(1)
DNA microarrays	54	(3)
Mass spectrometry	57	(5)
Computing in protein science	62	(6)
Computer-based instrumentation	62	(1)
Simulations, including molecular dynamics	63	(1)
Molecular graphics	64	(1)
Bioinformatics	65	(2)
Useful Web Sites	67	(1)
Recommended Reading	68	(1)
Exercises, Problems, and Weblems	68	(5)
The Chemical Structure and Activity of Proteins	73	(52)
The polypeptide chain and protein conformation	74	(1)
The amino acids	74	(3)
Protein main chain conformation	77	(2)
Side chain conformation	79	(1)
Rotamer libraries	80	(1)
Stabilization of the native state	80	(6)
Spectroscopic methods of characterizing proteins in solution	86	(7)
Absorbance and fluorescence of proteins	89	(1)
Fluorescence is sensitive to the environment and dynamics of the chromophore	90	(1)
Fluorescence resonance energy transfer (FRET)	91	(1)
Circular dichroism	91	(2)
Protein structure determination	93	(6)
X-ray crystallography	95	(2)
Nuclear magnetic resonance spectroscopy (NMR)	97	(1)
Low-temperature electron microscopy (cryoEM)	98	(1)
The relationship between structure determinations of isolated proteins, and protein structure and function in vivo	99	(1)
Protein--ligand interactions	100	(2)
Catalysis by enzymes	102	(2)
The Michaelis--Menten equation describes the velocity of enzymatic reactions as a function of substrate concentration	102	(2)
Conformational change	104	(2)
The sliding filament mechanism of muscle contraction	105	(1)
Control of protein activity	106	(3)
Control of protein function: allosteric regulation	109	(8)
The allosteric change of haemoglobin	111	(5)
Useful Web Sites	116	(1)
Recommended Reading	116	(1)
Exercises, Problems, and Weblems	117	(8)
Evolution of Protein Structure and Function	125	(60)
Introduction	126	(7)
Protein structure classification	126	(7)
Secondary, tertiary, and quaternary structure	133	(2)
Domain swapping	135	(1)
Classifications of protein folding patterns	135	(5)
Catalogues of protein structures	135	(1)
Structural Classification of Proteins (SCOP)	136	(2)
FSSP and the DALI domain dictionary	138	(2)
Structural relationships among homologous proteins	140	(2)
Changes in proteins during evolution give clues to the roles of residues at different positions	142	(1)
Evolution of the globins	143	(7)
Mammalian globins	144	(3)
The structures of globins	147	(2)
Truncated globins	149	(1)
Evolution of NAD-binding domains of dehydrogenases	150	(7)
Comparison of NAD-binding domains of dehydrogenases	152	(5)
Evolution of visual pigments and related molecules	157	(7)
Selection and vertebrate opsins	162	(2)
How do proteins evolve new functions?	164	(6)
Directed evolution	169	(1)
Classification of protein functions	170	(7)
The Enzyme Commission (EC) classification	173	(2)
The Gene Ontology Consortium™	175	(1)
Useful Web Sites	175	(2)
Recommended Reading	177	(1)
Exercises, Problems, and Weblems	177	(8)
Protein Engineering, Folding, Prediction, and Design	185	(36)
The significance of protein engineering	185	(1)
Protein folding	186	(2)
Thermodynamics and kinetics---key concepts	188	(4)
Entropy	188	(1)
Spontaneity and equilibrium	189	(1)
Kinetics	190	(1)
Thermodynamics of the protein folding transition	191	(1)
Thermodynamics of mutated proteins	192	(1)
The effect of denaturants on rates of folding and unfolding: chevron plots	192	(6)
The molten globule	198	(1)
The relationship between the structure and kinetics of folding: contact order	198	(1)
Folding funnels	199	(1)
Protein misfolding and the GroEL--GroES chaperone protein	200	(4)
The GroEL--GroES conformational change	202	(1)
Operational cycle	203	(1)
Protein structure prediction and modelling	204	(7)
Critical Assessment of Structure Prediction (CASP)	205	(1)
Homology modelling	206	(1)
Threading	207	(1)
Prediction of novel folds	208	(3)
Prediction of protein function	211	(2)
Sometimes specific constellations of residues provide signature patterns in the sequence that identify an active site	212	(1)
Structural data provide additional routes to function prediction	212	(1)
Interaction patterns, contextual information, and intergenomic comparisons are useful indicators of function	213	(1)
Protein design	213	(3)
Useful Web Sites	215	(1)
Recommended Reading	215	(1)
Exercises, Problems, and Weblem	216	(5)
Proteins with Partners	221	(34)
Introduction	221	(2)
General properties of protein--protein interfaces	223	(3)
Burial of protein surface	223	(1)
The composition of the interface	224	(1)
Complementarity	224	(1)
Specific interactions at protein--protein interfaces	224	(2)
Multisubunit proteins	226	(1)
Protein--DNA interactions	227	(3)
Structural themes in protein--DNA binding and sequence recognition	228	(2)
Some protein--DNA complexes that regulate gene transcription	230	(7)
λ cro	230	(2)
The eukaryotic homeodomain antennapedia	232	(1)
Leucine zippers as transcriptional regulators	233	(1)
Zinc fingers	233	(1)
The E. coli Met repressor	234	(1)
The TATA-box binding protein	234	(1)
p53 is a tumour suppressor	235	(2)
Virus structures	237	(6)
Tomato bushy stunt virus (TBSV)	241	(1)
Bacteriophage HK97: protein chain-mail	242	(1)
The photosynthetic reaction centre	243	(4)
Membrane transport	247	(1)
Specificity of the potassium channel from Streptomyces lividans---room to swing a cation?	247	(1)
ATPase	248	(4)
Useful Web Sites	251	(1)
Recommended Reading	251	(1)
Exercises, Problems, and Weblems	252	(3)
Proteins in Disease	255	(36)
Introduction	256	(2)
Diseases of protein aggregation	258	(5)
Amyloidoses	258	(1)
Alzheimer disease	259	(2)
Parkinson disease	261	(1)
Huntington disease	261	(1)
Prion diseases---spongiform encephalopathies	261	(2)
Serpins: SERine Protease INhibitorS---conformational disease	263	(3)
Conformational states	263	(3)
Mechanism of protease inhibition by serpins	266	(1)
The immune system	266	(1)
Antibody structure	267	(7)
The constant, the variable, and the hypervariable	269	(1)
The antigen-binding site	270	(1)
Conformations of antigen-binding loops of antibodies	271	(2)
Greater variability in the H3 loop	273	(1)
Somatic mutation and the maturation of the antibody response	273	(1)
Proteins of the major histocompatibility complex (MHC)	274	(8)
Structures of MHC proteins	276	(3)
Specificities of the MHC system	279	(1)
Class I and class II MHC proteins function in parallel, selecting different immune responses to extracellular and intracellular pathogens	280	(1)
Peptide binding	280	(2)
T-cell receptors	282	(1)
The TCR--MHC--peptide complex	282	(1)
Cancer	283	(5)
Malfunctions in two classes of genes contribute to the development of cancer	284	(1)
Viruses and cancer	285	(1)
Cancer and protein structures	285	(1)
Useful Web Sites	286	(1)
Recommended Reading	286	(2)
Exercises, Problems, and Weblems	288	(3)
Epilogue	291	(2)
Abbreviations	293	(4)
Glossary	297	(10)
Index	307