Chaperones (Topics in Current Genetics)

Front......Page 1
Foreword......Page 5
Table of contents......Page 6
List of contributors......Page 11
1 Preface......Page 14
2 Transcriptional regulation of the heat shock response in bacteria......Page 15
3 Regulation of the eukaryotic heat shock response via heat shock elements......Page 16
4 Heat shock factors constitute a conserved family of transcriptional regulators......Page 17
5.1 Modular structure of HSF1......Page 20
5.3 Complex regulation of HSF1 transcriptional activity by posttranslational modifications......Page 21
5.4 Interactions between HSF1 and the transcriptional machinery......Page 24
5.5 Negative and positive regulation of HSF1 by interacting proteins......Page 25
5.6 Role of HSF1 in normal development and physiology......Page 27
6 HSF2 – a cooperative modulator of HSF1?......Page 28
7 HSF3 – an avian-specific regulator of heat shock genes......Page 30
9.1 Broad repertoire of HSF target genes......Page 31
9.2 Regulation of longevity by HSF1......Page 33
9.3 HSF1-dependent transcription of satellite III repeats previously considered as heterochromatin......Page 34
10 Conclusions and perspectives......Page 35
References......Page 36
1 Endoplasmic reticulum (ER): the journey to secretion......Page 48
2.2 Non-conventional HAC1 mRNA splicing......Page 50
2.4 UPR specific transcription factors in yeast......Page 52
3.1 IRE1......Page 53
3.2 ATF6......Page 55
3.3 PERK......Page 56
3.4 Transcriptional output of three UPR signaling branches......Page 59
4 Phospholipids and the UPR......Page 60
5 UPR signaling arm specific components identified to date......Page 61
5.2 PERK signaling branch......Page 62
6 BiP associates with the luminal domains of IRE1, PERK, and ATF6......Page 63
7 Time dependent shift of the UPR response......Page 64
8 Physiological roles of the UPR......Page 65
9 Conclusions......Page 66
References......Page 67
1 Hsp104p and thermotolerance in yeast......Page 77
2 In vitro reconstitution of Hsp104p refolding activity......Page 80
3 Hsp100 structure and function......Page 82
4 Mechanism of protein disaggregation......Page 85
5 Organization of the bichaperone network......Page 88
6 Yeast prions and Hsp104p......Page 89
7 Implications for protein aggregation disease......Page 94
References......Page 96
1 The scope of protein folding in the ER......Page 103
2 Entry into the ER......Page 104
4 Signal peptide cleavage......Page 105
5 The proline problem......Page 107
6 Folding of ER glycoproteins......Page 108
8 Disulfide bond formation......Page 112
10 Folding of specialised proteins in the ER......Page 116
11 Techniques, model systems and what’s next......Page 118
References......Page 119
1 Stability of mitochondria......Page 130
2 Molecular chaperone proteins and mitochondrial proteolysis......Page 132
3 ATP-dependent proteases of mitochondria......Page 133
3.1.2 Functions of Lon proteases within mitochondria......Page 135
3.2 Mitochondrial Clp proteases......Page 137
3.3.1 The family of AAA proteases......Page 138
3.3.2 Roles of AAA proteases in mitochondria......Page 139
4 Quality control of inner membrane proteins......Page 142
4.1 Substrate recognition by AAA proteases......Page 143
4.2 Substrate dislocation during proteolysis by AAA proteases......Page 144
5 Regulation of quality control systems of mitochondria......Page 147
References......Page 148
1 Introduction......Page 159
2.1 Formation, maintenance, and function......Page 160
2.3.1 PTS1 protein import......Page 163
2.3.2 PTS2 protein import......Page 164
2.4 Formation of peroxisomes......Page 165
2.5.2 The Pex5p extended shuttle......Page 166
2.5.3 The Pex7p shuttle......Page 167
2.6 Docking and translocation of peroxisomal proteins......Page 168
2.7 Folding state and import of peroxisomal proteins......Page 170
3.1 Hsp70 family introduction......Page 172
3.2 In vivo roles of Hsp70......Page 175
3.3 Hsp70 and import of proteins into organelles......Page 176
3.4 Hsp70 and peroxisomal protein import......Page 178
4.2 In vivo roles of Hsp90......Page 180
4.3 Hsp90 and import of proteins into organelles......Page 181
5 Concluding remarks......Page 182
References......Page 183
1 Introduction......Page 194
2.1 Hsp70 and Hsp90 chaperones – protein folding and re-folding......Page 195
2.2 The ubiquitin-proteasome system......Page 198
2.3.1 CHIP – a conductor of protein degradation in the cytosol......Page 200
2.3.2 U-box ligases serve multiple functions......Page 203
3.2 The ER-associated protein degradation pathway......Page 204
3.3.1 What makes a protein a substrate of the degradation system?......Page 205
3.3.2 A single pathway for all substrates?......Page 207
3.4 Dislocation of terminally misfolded proteins......Page 209
3.6 Do E3 ligases play a central role in the ER degradation system?......Page 211
4 Cdc48p/p97 – chaperoning poly-ubiquitinated proteins......Page 213
5 Diseases and toxins – what can go wrong in protein degradation?......Page 215
5.1 Diseases associated with protein degradation......Page 216
5.2 Viruses and AB-toxins......Page 217
5.3 Pharmacological chaperones – a new approach in fighting folding diseases......Page 218
6 Conclusions......Page 220
References......Page 221
1 Prion diseases......Page 230
3.2 Structure......Page 231
3.4 Function......Page 232
4 The prions in yeast and fungi......Page 233
4.2.1 The [PSI+] and [PIN] phenotypes......Page 234
4.2.3 The [Het-s] phenotype......Page 236
4.3 Structural features......Page 237
5 Properties of the fibrillar forms of prion proteins......Page 238
7 Mechanistic models for prion propagation......Page 240
8 Maintenance and inheritance......Page 241
9 In vitro assembly process of prions proteins......Page 243
10 Prions and misfolding diseases, unquestioned issues, and unanswered questions......Page 246
References......Page 248
1.1 Introduction......Page 260
2.1 GroEL structure......Page 263
2.3 The structure of the GroEL-ATP complex......Page 264
2.4 The structure of the GroEL-GroES complexes......Page 265
4 Allostery and asymmetry in nucleotide binding to GroEL......Page 266
5.1 Substrate binding to GroEL......Page 268
5.2 Encapsulation and the initiation of protein folding......Page 270
5.4 Ejection of the substrate and GroES from the cis ring......Page 271
6 The Group I chaperonin-assisted protein folding reaction......Page 272
7.1 Introduction......Page 273
8 Group II chaperonin subunit composition and organization......Page 275
9 Structure of the Group II chaperonins......Page 276
10 Nucleotide-induced structural rearrangements in the Group II chaperonins......Page 278
11 Allostery in the Group II chaperonins......Page 280
12 Interaction between the Group II chaperonins and protein substrates......Page 282
13 Future perspectives......Page 283
References......Page 284
Index......Page 293