Chaperones: 16

309 Pages·2006·9.827 MB·English

by  Ville Hietakangas, Lea Sistonen (auth.), Ineke Braakman (eds.)

16
Topics in Current Genetics
Series Editor:Stefan Hohmann
Marja Makarow • Ineke Braakman (Eds.)
Chaperones
With 43 Figures,1 in Color;and 3 Tables
AB C
Professor Dr.Marja Makarow
Department ofBiotechnology
P.O.Box 56
00014 Helsinki University
Helsinki
Finland
Professor Dr.Ineke Braakman
Universiteit Utrecht
Faculty ofScience
P.O.Box 80083
3508 TB Utrecht
The Netherlands
The cover illustration depicts pseudohyphal filaments of the ascomycete Saccharomyces cerevisiae
that enable this organism to forage for nutrients.Pseudohyphal filaments were induced here in a wild-
type haploid MATa S1278b strain by an unknown readily diffusible factor provided by growth in con-
frontation with an isogenic petite yeast strain in a sealed petri dish for two weeks and photographed
at 100X magnification (provided by Xuewen Pan and Joseph Heitman).
ISSN 1610-2096
ISBN-10 3-540-32580-8 Springer Berlin Heidelberg New York
ISBN-13 978-3-540-32580-2
Library ofCongress Control Number:2006920789
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Foreword VII
Foreword
Ineke Braakman and Marja Makarow
Molecular chaperones interact with virtually every newly synthesized protein.
Their role is not limited to this, as an increasing number of protein-protein interac-
tions are found to be mediated by molecular chaperones. They reside in large
complexes, in every cellular compartment, and to some extent even outside cells.
These proteins are of interest to a large number of scientists, not only to those in-
terested in protein biosynthesis, but also in relation to protein transport, organelle
biogenesis, and cell stress. Molecular chaperones have entered textbooks in Cell
Biology and Biochemistry, and many undergraduate and graduate students are
taught about the chaperone cycles of substrate binding and release and the co-
chaperones that regulate a chaperone's activity.
Whereas excellent reviews on molecular chaperones are published, they often
focus on the latest results without reiterating the basics. These reviews are impor-
tant, but often too advanced to be useful for students and scientist who want to en-
ter the chaperone field. Goal of this issue was to assemble a collection of reviews
on molecular chaperones that would be both timely and basic, which would make
them an excellent entrance for novices into the field and suitable for teaching pur-
poses. The reviews together do not cover the complete field of chaperones but in-
stead focus on one particular chaperone or one particular organelle or process.
This still allows a both broad and deep coverage of each topic, but also gives an
impression of the wealth of processes molecular chaperones are involved in.
We feel to have succeeded in the task we set ourselves, and thank all authors
for their contributions. We hope that you will enjoy reading this issue as much as
we enjoyed planning and assembling it.

Braakman, Ineke
Professor of Cellular Protein Chemistry, University of Utrecht, The Nether-
lands
[email protected]

Makarow, Marja
Professor of Applied Biochemistry and Molecular Biology, University of Hel-
sinki, Finland
[email protected]
Table of contents
Regulation of the heat shock response by heat shock transcription factors.....1
Ville Hietakangas and Lea Sistonen..................................................................1
Abstract.........................................................................................................1
1 Preface........................................................................................................1
2 Transcriptional regulation of the heat shock response in bacteria..............2
3 Regulation of the eukaryotic heat shock response via heat shock
elements.........................................................................................................3
4 Heat shock factors constitute a conserved family of transcriptional
regulators.......................................................................................................4
5 HSF1 – the prototypical heat shock transcription factor............................7
5.1 Modular structure of HSF1.................................................................7
5.2 Rapid and transient HSF1 DNA-binding activity in response
to stress.....................................................................................................8
5.3 Complex regulation of HSF1 transcriptional activity by post-
translational modifications........................................................................8
5.4 Interactions between HSF1 and the transcriptional machinery.........11
5.5 Negative and positive regulation of HSF1 by interacting proteins...12
5.6 Role of HSF1 in normal development and physiology.....................14
6 HSF2 – a cooperative modulator of HSF1?..............................................15
7 HSF3 – an avian-specific regulator of heat shock genes..........................17
8 HSF4 – regulator of eye development......................................................18
9 Novel functions for HSFs in transcription................................................18
9.1 Broad repertoire of HSF target genes...............................................18
9.2 Regulation of longevity by HSF1.....................................................20
9.3 HSF1-dependent transcription of satellite III repeats previously
considered as heterochromatin................................................................21
10 Conclusions and perspectives.................................................................22
Acknowledgements.....................................................................................23
References...................................................................................................23
The unfolded protein response unfolds..............................................................35
Maho Niwa......................................................................................................35
Abstract.......................................................................................................35
1 Endoplasmic reticulum (ER): the journey to secretion.............................35
2 The unfolded protein response (UPR) pathway........................................37
2.1 Yeast UPR........................................................................................37
2.2 Non-conventional HAC1 mRNA splicing........................................37
2.3 Are there additional RNA substrates for yeast Ire1p?.......................39
2.4 UPR specific transcription factors in yeast.......................................39
3 Mammalian UPR......................................................................................40
3.1 IRE1..................................................................................................40
X Table of contents
3.2 ATF6.................................................................................................42
3.3 PERK................................................................................................43
3.4 Transcriptional output of three UPR signaling branches..................46
4 Phospholipids and the UPR......................................................................47
5 UPR signaling arm specific components identified to date......................48
5.1 IRE1 signaling branch......................................................................49
5.2 PERK signaling branch.....................................................................49
5.3 ATF6 signaling branch.....................................................................50
6 BiP associates with the luminal domains of IRE1, PERK, and ATF6.....50
7 Time dependent shift of the UPR response..............................................51
8 Physiological roles of the UPR................................................................52
9 Conclusions..............................................................................................53
Acknowledgements.....................................................................................54
References...................................................................................................54
Hsp104p: a protein disaggregase.......................................................................65
Johnny M. Tkach and John R. Glover.............................................................65
Abstract.......................................................................................................65
1 Hsp104p and thermotolerance in yeast....................................................65
2 In vitro reconstitution of Hsp104p refolding activity...............................68
3 Hsp100 structure and function.................................................................70
4 Mechanism of protein disaggregation......................................................73
5 Organization of the bichaperone network................................................76
6 Yeast prions and Hsp104p........................................................................77
7 Implications for protein aggregation disease............................................82
8 Final Remarks..........................................................................................84
References...................................................................................................84
Folding of newly synthesised proteins in the endoplasmic reticulum.............91
Sanjika Dias-Gunasekara and Adam M. Benham............................................91
Abstract.......................................................................................................91
1 The scope of protein folding in the ER....................................................91
2 Entry into the ER......................................................................................92
3 ER protein sorting....................................................................................93
4 Signal peptide cleavage............................................................................93
5 The proline problem.................................................................................95
6 Folding of ER glycoproteins....................................................................96
7 BiP..........................................................................................................100
8 Disulfide bond formation.......................................................................100
9 Introducing more ER chaperones...........................................................104
10 Folding of specialised proteins in the ER.............................................104
11 Techniques, model systems and what’s next........................................106
Acknowledgements...................................................................................107
References.................................................................................................107
Abbreviations............................................................................................116
Table of contents XI
Quality control of proteins in the mitochondrion...........................................119
Mark Nolden, Brigitte Kisters-Woike, Thomas Langer, and Martin Graef...119
Abstract.....................................................................................................119
1 Stability of mitochondria........................................................................119
2 Molecular chaperone proteins and mitochondrial proteolysis................121
3 ATP-dependent proteases of mitochondria............................................122
3.1 Mitochondrial Lon proteases..........................................................124
3.2 Mitochondrial Clp proteases...........................................................126
3.3 AAA proteases in the inner membrane...........................................127
4 Quality control of inner membrane proteins...........................................131
4.1 Substrate recognition by AAA proteases........................................132
4.2 Substrate dislocation during proteolysis by AAA proteases...........133
4.3 Additional components of the quality control system.....................136
5 Regulation of quality control systems of mitochondria..........................136
References.................................................................................................137
Chaperone proteins and peroxisomal protein import....................................149
Wim de Jonge, Henk F. Tabak, and Ineke Braakman....................................149
Abstract.....................................................................................................149
1 Introduction............................................................................................149
2 Peroxisomes...........................................................................................150
2.1 Formation, maintenance, and function............................................150
2.2 General properties of protein import...............................................153
2.3 Proteins involved in protein import................................................153
2.4 Formation of peroxisomes..............................................................155
2.5 Recycling receptor import model....................................................156
2.6 Docking and translocation of peroxisomal proteins........................158
2.7 Folding state and import of peroxisomal proteins...........................160
3 Involvement of Hsp70 in peroxisomal protein import...........................162
3.1 Hsp70 family introduction..............................................................162
3.2 In vivo roles of Hsp70.....................................................................165
3.3 Hsp70 and import of proteins into organelles.................................166
3.4 Hsp70 and peroxisomal protein import...........................................168
4 Involvement of Hsp90 in peroxisomal protein import...........................170
4.1 Hsp90 family introduction..............................................................170
4.2 In vivo roles of Hsp90.....................................................................170
4.3 Hsp90 and import of proteins into organelles.................................171
4.4 Hsp90 and peroxisomal protein import...........................................172
5 Concluding remarks...............................................................................172
References.................................................................................................173
Proteasomal degradation of misfolded proteins.............................................185
Robert Gauss, Oliver Neuber, and Thomas Sommer.....................................185
Abstract.....................................................................................................185
1 Introduction............................................................................................185
2 Recognition and degradation of aberrant proteins in the cytosol...........186
XII Table of contents
2.1 Hsp70 and Hsp90 chaperones – protein folding and re-folding......186
2.2 The ubiquitin-proteasome system...................................................189
2.3 Some U-box ligases link chaperones to the ubiquitin-
proteasome system................................................................................191
3 Protein degradation from the ER............................................................195
3.1 Quality control in the ER and the unfolded protein response.........195
3.2 The ER-associated protein degradation pathway............................195
3.3 Selection and recruitment of aberrant proteins...............................196
3.4 Dislocation of terminally misfolded proteins..................................200
3.5 Ubiquitination of aberrant ER-resident proteins.............................202
3.6 Do E3 ligases play a central role in the ER degradation system?...202
3.7 Driving-force of dislocation............................................................204
4 Cdc48p/p97 – chaperoning poly-ubiquitinated proteins........................204
5 Diseases and toxins – what can go wrong in protein degradation?........206
5.1 Diseases associated with protein degradation.................................207
5.2 Viruses and AB-toxins....................................................................208
5.3 Pharmacological chaperones – a new approach in fighting
folding diseases.....................................................................................209
6 Conclusions............................................................................................211
Acknowledgement.....................................................................................211
References.................................................................................................212
Template-induced protein misfolding underlying prion diseases.................221
Luc Bousset, Nicolas Fay, and Ronald Melki................................................221
Abstract.....................................................................................................221
1 Prion diseases.........................................................................................221
2 Formulation of the prion hypothesis......................................................222
3 The mammalian prion PrP......................................................................222
3.1 Identification...................................................................................222
3.2 Structure..........................................................................................222
3.3 Folding properties...........................................................................223
3.4 Function..........................................................................................223
3.5 Cellular processing.........................................................................224
4 The prions in yeast and fungi.................................................................224
4.1 Genetic criteria for the prions in yeast and fungi............................225
4.2 Characteristics................................................................................225
4.3 Structural features...........................................................................228
5 Properties of the fibrillar forms of prion proteins...................................229
6 Soluble oligomeric forms of the prion proteins......................................231
7 Mechanistic models for prion propagation.............................................231
8 Maintenance and inheritance..................................................................232
9 In vitro assembly process of prions proteins..........................................234
10 Prions and misfolding diseases, unquestioned issues, and
unanswered questions................................................................................237
11 Conclusions and perspectives...............................................................239
References.................................................................................................239
Table of contents XIII
The Hsp60 chaperonins from prokaryotes and eukaryotes...........................251
M. Giulia Bigotti, Anthony R. Clarke, and Steven G. Burston......................251
Abstract.....................................................................................................251
1 The Group I chaperonins........................................................................251
1.1 Introduction.....................................................................................251
2 Structure of the Group I chaperonins.....................................................254
2.1 GroEL structure..............................................................................254
2.2 GroES structure...............................................................................255
2.3 The structure of the GroEL-ATP complex......................................255
2.4 The structure of the GroEL-GroES complexes...............................256
3 Interaction between Group I chaperonins and protein substrate.............257
4 Allostery and asymmetry in nucleotide binding to GroEL.....................257
5 Reaction cycle of the Group I chaperonins............................................259
5.2 Encapsulation and the initiation of protein folding.........................261
5.3 Priming the complex for the release of GroES and polypeptide
substrate................................................................................................262
5.4 Ejection of the substrate and GroES from the cis ring....................262
6 The Group I chaperonin-assisted protein folding reaction.....................263
7 The Group II chaperonins.......................................................................264
7.1 Introduction.....................................................................................264
8 Group II chaperonin subunit composition and organization..................266
9 Structure of the Group II chaperonins....................................................267
10 Nucleotide-induced structural rearrangements in the Group II
chaperonins...............................................................................................269
11 Allostery in the Group II chaperonins..................................................271
12 Interaction between the Group II chaperonins and protein substrates..273
13 Future perspectives...............................................................................274
References.................................................................................................275
Index...................................................................................................................285