Frishman Structural Bioinformatics of Membrane Proteins

1. Auflage 2011
ISBN: 978-3-7091-0045-5
Verlag: Springer Vienna
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 281 Seiten

This book is the first one specifically dedicated to the structural bioinformatics of membrane proteins. With a focus on membrane proteins from the perspective of bioinformatics, the present work covers a broad spectrum of topics in evolution, structure, function, and bioinformatics of membrane proteins focusing on the most recent experimental results. Leaders in the field who have recently reported breakthrough advances cover algorithms, databases and their applications to the subject. The increasing number of recently solved membrane protein structures makes the expert coverage presented here very timely. Structural bioinformatics of membrane proteins has been an active area of research over the last thee decades and proves to be a growing field of interest.

Autoren/Hrsg.

Frishman, D.

Inhaltsverzeichnis

1;Title Page ;2
2;Copyright Page ;3
3;Table of Contents ;4
4;Evolutionary origins of membrane proteins;11
4.1;1 Introduction;11
4.2;2 Comparative analysis of F/V-type ATPases: example of function cooption?;13
4.3;3 Emergence of integral membrane proteins;19
4.4;4 Emergence of lipid membranes;20
4.5;5 Scenario for the origin and evolution of membranes and membrane proteins;27
4.6;Acknowledgments;31
4.7;References;31
5;Molecular archeological studies of transmembrane transport systems;39
5.1;1 Introduction;39
5.2;2 Molecular transport;40
5.3;3 Techniques to establish homology or the lack of homology;40
5.4;4 Transport protein diversity;41
5.5;5 The ABC superfamily;42
5.6;6 Independent origins for ABC porters;43
5.7;7 The phosphoenolpyruvate-dependent sugar transporting phosphotransferase system (PTS);45
5.8;8 Independent origins for PTS permeases;47
5.9;9 Reverse (retro)-evolution;48
5.10;10 Conclusions and perspectives;50
5.11;References;51
6;Resource for structure related information on transmembrane proteins;54
6.1;1 Introduction;54
6.2;2 3D structure resources;55
6.2.1;2.1 Protein Data Bank;55
6.2.2;2.2 Manually curated structure resources of TMPs;56
6.2.3;2.3 TMDET algorithm;57
6.2.4;2.4 PDBTM database;60
6.2.5;2.5 OPM database;61
6.2.6;2.6 Modeling protein–lipid assembly;61
6.3;3 2D structure resources;62
6.3.1;3.1 TOPDB database;63
6.3.2;3.2 TOPDOM database;64
6.3.3;3.3 Prediction methods incorporating experimental results;65
6.4;Acknowledgments;66
6.5;References;66
7;Topology prediction of membrane proteins: how distantly related homologs come into play;69
7.1;1 Introduction;69
7.2;2 From membrane protein sequence to topologic models;70
7.2.1;2.1 Datasets of membrane proteins;71
7.2.2;2.2 Scoring the accuracy of diff erent methods;72
7.2.3;2.3 Propensity scales versus machine learning-based methods;73
7.2.4;2.4 Methods for optimizing topologic models;74
7.2.5;2.5 Single sequence versus multiple sequence profi le;76
7.2.6;2.6 Prediction of signal peptides and GPI-anchors;77
7.2.7;2.7 More methods are bett er than one: CINTHIA;77
7.2.8;2.8 A large-scale annotator of the human proteome: the PONGO system;79
7.3;3 From membrane protein sequence to function and structure;81
7.3.1;3.1 Membrane proteins: how many with known functions and folds?;82
7.3.1.1;3.1.1 All-alpha membrane proteins;82
7.3.1.2;3.1.2 All-beta membrane proteins;83
7.3.2;3.2 What do BAR clusters contain?;84
7.3.2.1;3.2.1 The cluster of glyceroporins;84
7.3.2.2;3.2.2 The cluster of multidrug transporter proteins (EmrE proteins);86
7.3.2.3;3.3.3 The cluster of P-glycoproteins;88
7.4;References;88
8;Transmembrane beta-barrel protein structure prediction;91
8.1;1 Introduction;91
8.1.1;1.1 1D feature prediction;92
8.1.2;1.2 ß-Contact and tertiary structure prediction;92
8.2;2 Data;93
8.2.1;2.1 Benchmark sets;93
8.2.2;2.2 Cross-validation;95
8.2.3;2.3 Template construction;95
8.3;3 Methods;95
8.3.1;3.1 Secondary structure prediction;95
8.3.1.1;3.1.1 Neural network implementation;95
8.3.1.2;3.1.2 Two-class prediction (ß, –);96
8.3.1.3;3.1.3 Three-class prediction (M, C, –);97
8.3.2;3.2 ß-Contact prediction;98
8.3.3;3.3 Tertiary structure prediction;98
8.3.3.1;3.3.1 Search energy;98
8.3.3.2;3.3.2 Template usage;99
8.3.3.3;3.3.3 Move types;100
8.3.3.4;3.3.4 Conformational search;101
8.4;4 Results;101
8.4.1;4.1 Secondary structure prediction results;101
8.4.1.1;4.1.1 Secondary structure evaluation metrics;101
8.4.1.2;4.1.2 Results using SetTransfold;102
8.4.1.3;4.1.3 Results using SetPRED-TMBB;103
8.4.2;4.2 ß-Contact prediction results;103
8.4.2.1;4.2.1 ß-Contact evaluation metrics;103
8.4.2.2;4.2.2 Results using SetTransfold;104
8.4.2.3;4.2.3 Results using SetPRED-TMBB;104
8.4.3;4.3 Tertiary structure prediction results;104
8.4.3.1;4.3.1 Tertiary structure evaluation metrics;105
8.4.3.2;4.3.2 Prediction results;106
8.4.3.3;4.3.3 Self-consistency results;106
8.5;5 Discussion;107
8.6;References;107
9;Multiple alignment of transmembrane protein sequences;111
9.1;1 Introduction;111
9.2;2 Factors influencing the alignment of transmembrane proteins;113
9.2.1;2.1 Transmembrane substitution rates;113
9.2.2;2.2 Transmembrane alignment gaps;115
9.3;3 Overview of TM MSA methods;115
9.3.1;3.1 TM-aware multiple sequence alignment by the Praline method;116
9.3.1.1;3.1.1 Profile pre-processing;116
9.3.1.2;3.1.2 Bipartite alignment scheme;117
9.3.1.3;3.1.3 Tree-based consistency iteration;118
9.3.2;3.2 Bipartite MSA compared to standard MSA;119
9.3.3;3.3 Comparing PRA LINE-TM with non-TM MSA methods;120
9.4;4 Benchmarking transmembrane alignments;122
9.4.1;4.1 Defi ning TM regions;123
9.5;5 Applications for TM multiple alignments;124
9.5.1;5.1 Homology searches of TM proteins;125
9.6;6 Current bottlenecks;125
9.7;7 Avenues for improvement;126
9.8;8 Conclusions;127
9.9;References;127
10;Prediction of re-entrant regions and other structural features beyond traditional topology models;131
10.1;1 Introduction;131
10.2;2 Background;133
10.2.1;2.1 The Z-coordinate as a measure of distance to the membrane;133
10.3;3 Interface helices;133
10.3.1;3.1 Prediction of interface helices;135
10.3.2;3.2 Prediction of amphipathic membrane anchors;136
10.4;4 Helical kinks in transmembrane helices;136
10.4.1;4.1 Prediction of helix kinks;137
10.5;5 Re-entrant regions;137
10.5.1;5.1 Prediction of re-entrant regions;138
10.5.1.1;5.1.1 TOP-MOD;138
10.5.1.2;5.1.2 TMloop;139
10.5.1.3;5.1.3 OCTOPUS;139
10.5.1.4;5.1.4 MEMSAT-SVM;139
10.6;6 Prediction of the Z-coordinate;140
10.7;7 Free energy of membrane insertion .G;141
10.8;8 The frequency of re-entrant regions and interface helices;142
10.9;9 Summary;143
10.10;References;143
11;Dual-topology: one sequence, two topologies;145
11.1;1 Introduction;145
11.2;2 Background;147
11.2.1;2.1 A brief history of dual-topology research;147
11.2.2;2.2 The difference between dual- and multiple-topology;147
11.2.3;2.3 Topology mapping;147
11.2.4;2.4 Arginines and lysines are important for the topology;148
11.2.5;2.5 Internal structural repeats – evidence of former gene duplication events;148
11.3;3 Prediction of dual-topology;150
11.3.1;3.1 The small multidrug resistance family: one family, different topologies;150
11.3.2;3.2 The DUF606 family contains fused genes;151
11.4;4 Examples of membrane proteins with dual- or multiple-topology;152
11.4.1;4.1 MRAP;152
11.4.2;4.2 Ductin;152
11.4.3;4.3 Hepatitis B virus L protein;153
11.4.4;4.4 Hepatitis C virus protein NS4B;154
11.4.5;4.5 TatA;154
11.4.6;4.6 PrP;155
11.5;5 Using topology inversion for function;155
11.5.1;5.1 SecG;155
11.6;6 Using dual-topology as a targeting system;156
11.6.1;6.1 Cytochrome p450-2E1;156
11.6.2;6.2 Epoxide hydrolase;156
11.7;References;156
12;Predicting the burial/exposure status of transmembrane residues in helical membrane proteins;159
12.1;1 Introduction;159
12.2;2 Hydrophobicity analysis;162
12.3;3 Amino acid propensity scales;163
12.4;4 Methods using sequence conservation;166
12.5;5 Applications of burial prediction;170
12.6;References;171
13;Helix–helix interaction patt erns in membrane proteins;173
13.1;1 Introduction;173
13.2;2 Technical approaches to identify transmembrane helix–helix interfaces;175
13.3;3 Structure of transmembrane helix–helix interfaces;178
13.3.1;3.1 Amino acid side-chain packing;178
13.3.2;3.2 GxxxG motifs;179
13.3.3;3.3 Hydrogen bonding;181
13.3.4;3.4 Charge–charge interactions;182
13.3.5;3.5 Aromatic interactions;184
13.4;4 Dynamic TMD–TMD interactions;185
13.5;Acknowledgments;186
13.6;References;187
14;Predicting residue and helix contacts in membrane proteins;195
14.1;1 Introduction;195
14.2;2 Biological background;196
14.2.1;2.1 Diversity of helix–helix contacts in membrane proteins;197
14.2.2;2.2 Frequency of residue contacts in membrane and soluble proteins;198
14.3;3 Prediction of lipid accessibility;199
14.3.1;3.1 Hydrophobicity-based predictions;199
14.3.2;3.2 Amino acid propensity scales derived from membrane protein sequences and structures;200
14.3.3;3.3 Sequence conservation of exposed and buried transmembrane residues;201
14.3.4;3.4 Best performing methods in the field of lipid accessibility;201
14.4;4 Prediction of helix–helix contacts;202
14.4.1;4.1 Co-evolving residues in membrane proteins;202
14.4.2;4.2 Prediction of helix–helix contacts with machine-learning techniques;203
14.5;5 Prediction of helix interactions;205
14.6;6 Modeling of membrane proteins with predicted contact information;207
14.7;Acknowledgement;209
14.8;References;209
15;Natural constraints, folding, motion, and structural stability in transmembrane helical proteins;212
15.1;1 Folding background;212
15.1.1;1.1 Two-stage hypothesis;212
15.1.2;1.2 Translocon-aided folding;213
15.2;2 Overview of non-interhelical stabilizing forces and natural constraints;213
15.2.1;2.1 Membrane constraints and interactions;213
15.2.1.1;2.1.1 Hydrophobic mismatch;214
15.2.1.2;2.1.2 Specifi c fl anking and anchoring interactions with polar headgroups;214
15.2.1.3;2.1.3 Positive-inside rule;214
15.2.2;2.2 Loop constraints;214
15.3;3 Interhelical interactions and constraints;215
15.3.1;3.1 Helix–helix packing;215
15.3.2;3.2 Motifs and stabilizing specific interactions;215
15.3.2.1;3.2.1 Packing motifs;216
15.3.2.2;3.2.2 Hydrogen bonds;216
15.3.2.3;3.2.3 Aromatic interactions;216
15.3.2.4;3.2.4 Salt bridges;216
15.3.3;3.3 The five types of specific stabilizing interhelical interactions considered;216
15.3.4;3.4 Structural hot spots;217
15.3.5;3.5 Experimental data on residue contributions to stabilization;218
15.3.6;3.6 Particularly stabilizing interactions as geometric constraints;219
15.3.7;3.7 Helix pairs revisited;221
15.3.8;3.8 Constraint perspective and underlying rigid-body geometry;221
15.3.9;3.9 Iterative reassembly of full TM helix bundles using interactions of the five types;223
15.3.10;3.10 The sets of the five types of particularly favorable interactions determine the packing of helices in the native structures of a diverse test set;224
15.3.11;3.11 Distribution of particularly stabilizing residues, folding funnels, and the construction of low-energy minima;225
15.3.12;3.12 Cooperativity with packing;226
15.3.13;3.13 Static structures versus ensembles;226
15.4;4 Conservation and diversity of determining sets of stabilizing interactions;226
15.4.1;4.1 Conservation and diversity of the determining sets of interactions of bR;228
15.5;5 Determining sets, multiple states, and motion;228
15.5.1;5.1 Multiple states and motion in the ErbB family;229
15.6;6 Conclusion;232
15.7;References;232
16;Prediction of three-dimensional transmembrane helical protein structures;237
16.1;1 Introduction;237
16.2;2 Goal of the chapter;238
16.3;3 Methods;238
16.3.1;3.1 De novo membrane protein structure prediction;238
16.3.1.1;3.1.1 MP topology predictions;240
16.3.1.2;3.1.2 The first MP structure prediction methods developed during the past decade;240
16.3.1.3;3.1.3 Solutions to the conformational search problem: folding with predicted constraints and contact predictors;243
16.3.1.3.1;3.1.3.1 Folding with predicted constraints;243
16.3.1.3.2;3.1.3.2 Contact predictors;245
16.3.1.4;3.1.4 MP-specifi c energy functions for decoy discrimination;246
16.3.2;3.2 Sequence-based modeling with experimental constraints;247
16.3.3;3.3 Comparative modeling of MP structures;250
16.4;4 Conclusions and future directions;251
16.5;References;252
17;GPCRs: past, present, and future;256
17.1;1 Introduction;256
17.2;2 A short history;257
17.3;3 GPCR structures;264
17.3.1;3.1 Rhodopsin;264
17.3.2;3.2 Ligand-mediated GPCRs;266
17.4;4 From sequence to structure;271
17.4.1;4.1 The conserved cysteine bridge in the extracellular domain;271
17.4.2;4.2 Loop IV–V, cysteine bridges, and ligand binding;271
17.5;5 The future;275
17.6;References;278
18;LIST OF CONTRIBUTORS;284