Co-chaperones are important mediators of the outcome of chaperone assisted protein homeostasis, which is the dynamic integration of the processes of protein folding, degradation and translocation to ensure that cellular function is finely tuned in space and time.
This third edition of the book The Networking of Chaperones by Co-chaperones describes how the function of the major molecular chaperones is regulated by co-chaperones, a diverse cohort of non-client proteins. Since the second edition was released, not only has knowledge deepened on how co-chaperones act as nodes to network and functionalise chaperones, but an understanding of their broader biological function has started to emerge. The third edition provides new and updated chapters highlighting recent developments and emerging themes on co-chaperones, such as their extracellular functions, their role in human disease and their status as putative drug targets.
The book is a useful resource for both newcomers and established researchers in the field of cell stress and chaperones, as well as those interested in cross-cutting disciplines such as cellular networks and systems biology.
Author(s): Adrienne L. Edkins, Gregory L. Blatch
Series: Subcellular Biochemistry, 101
Edition: 3
Publisher: Springer
Year: 2022
Language: English
Pages: 435
City: Cham
Preface
Acknowledgements
Contents
Editors and Contributors
Chapter 1: Nucleotide Exchange Factors for Hsp70 Molecular Chaperones: GrpE, Hsp110/Grp170, HspBP1/Sil1, and BAG Domain Protei...
Introduction
Hsp70 Architecture and Functional Cycle
DnaK, DnaJ, and GrpE: The Eubacterial Hsp70 System
The Evolution of the Eukaryotic Hsp70 Systems
Molecular Structure and Function of Eukaryotic NEFs
Eukaryotic GrpE Homologs
The Hsp110 Family of Nucleotide Exchange Factors
Sil1/HspBP1 Homologs
BAG Domain-Containing NEFs
ADP Dissociation Inhibitors: Antagonists of Hsp70-NEF Function
Cellular Functions of NEF Proteins in S. cerevisiae
Aspects of NEF Function in Mammalian Protein Folding and Quality Control
Conclusions
References
Chapter 2: Functions of the Hsp90-Binding FKBP Immunophilins
Introduction
Structure/Function Relationships of Steroid Receptor-Associated FKBPs
Cellular and Physiological Functions of Hsp90-Associated FKBPs
FKBP52
FKBP51
TPR-Domain Immunophilins Regulate the Subcellular Localization of Soluble Proteins
Xap2
FKBP36
FKBP38
FKBPL
Plant FKBPs
Summary
References
Chapter 3: Hsp70/Hsp90 Organising Protein (Hop): Coordinating Much More than Chaperones
Assisted Protein Folding by the Hsp70/Hsp90 Chaperone Complex
Hop (Hsp70-Hsp90 Organising Protein)
Structure of Hop
Functions of Hop
Hop as a Co-chaperone for Hsp70 and Hsp90: A Shift in the Paradigm
Extracellular Hop Has Cytokine-Like Activity
Hop in Human Cellular Function and Disease
Cancer Cell Biology
Hop as a Therapeutic Target for Cancer
Developmental and Protein Folding Disorders
Parasitic Diseases
Conclusion
References
Chapter 4: Specification of Hsp70 Function by Hsp40 Co-chaperones
Introduction
A. Hsp70 Co-chaperone Activity of Hsp40s
B. How Does the J-Domain Regulate Client Binding by Hsp70
C. Do Hsp40s Act as Chaperones?
C. Determination of Hsp70 Functional Specificity
D. Hsp40 Quaternary Structure
E. ER-Transmembrane Hsp40s and Membrane Protein Quality Control
F. Hsp40s into the Future
References
Chapter 5: Cdc37 as a Co-chaperone to Hsp90
Introduction
Cdc37 in the Chaperoning of Protein Kinase
Structure and Interaction
Cdc37 in Cell Proliferation and Cancer
Cdc37 and Cancer Treatment
Roles for Cdc37 in Autophagy and Protein Aggregation Disorders
Conclusions
References
Chapter 6: p23 and Aha1: Distinct Functions Promote Client Maturation
The Conformational Cycle of Hsp90
The Hsp90 Co-chaperone p23
Discovery and Isoforms of p23
The Structure of p23
The Interaction of p23 with Hsp90
p23 and Hsp90 Client Maturation
Hsp90-Independent Functions of p23
The Intrinsic Chaperone Function of p23
The Nuclear Function of p23
Concluding Remarks
The Hsp90 Co-chaperone Aha1
Discovery and Isoforms of Aha1
The Structure of Aha1
The Interaction of Aha1 with Hsp90
Aha1 and Hsp90 Client Maturation
Integration of Aha1 and p23 into the Hsp90 ATPase Cycle
Conclusion
References
Chapter 7: Beyond Chaperoning: UCS Proteins Emerge as Regulators of Myosin-Mediated Cellular Processes
Introduction
UCS Proteins Are Indispensable for Myosin Folding but not Hsp90
Structural Organization and Versatility of UCS Proteins as Myosin Chaperones
UNC-45 Regulates Myosin Expression, Folding, Assembly, Contractile Function, and Degradation
UNC-45 Proteins in Invertebrates
UNC-45 Proteins in Vertebrates
UCS Proteins in Yeasts, Fungi, and Apicomplexans
UNC-45 and Cancers
Conclusions and Future Work
References
Chapter 8: Chaperonin: Co-chaperonin Interactions
Introduction
Activities of the E. coli GroEL/GroES Folding Machine
Structure of GroEL and GroES
The Role of GroES in the Reaction Cycle
Roles of Bacterial Chaperonins
Specific Functions of Bacterial Co-chaperonins
Roles of Eukaryotic Group I Chaperonins
Specific Functions of Eukaryotic Group I Co-chaperonins
Conclusion
References
Chapter 9: Co-chaperones of the Human Endoplasmic Reticulum: An Update
Introduction
The Chaperone Network of the Mammalian ER
The Hsp70/Hsp40 Chaperone Network of the Mammalian ER
The Two Hsp70s and NEFs of the Mammalian ER
The Functional Cycle of BiP
The Co-chaperones of BiP in the Mammalian ER
The Dual Role of BiP and Its Co-chaperone Sec63 in Protein Import into the ER as an Example of Chaperone/Co-chaperone Action i...
BiP Can Support Opening of the Human Sec61 Channel for ER Protein Import
BiP Can Support ER Protein Import by Acting as a Molecular Ratchet on the Incoming Precursor Polypeptide
Closing of the Human Sec61 Channel for Preservation of Cellular Calcium Homeostasis
Not All Hsp70s Are Created Equal: BiP and Kar2p Cannot Substitute for Each Other in Sec61 Channel Gating
Regulatory Mechanisms for the ER-Resident Hsp70/Hsp40 Chaperone Network
Nucleotide Transport Into and Out of the ER
Human Diseases Related to ER Chaperones or the Sec61 Channel: On Chaperonopathies and Sec61-Channelopathies
Conclusions and Open Questions
References
Chapter 10: J-Domain Proteins Orchestrate the Multifunctionality of Hsp70s in Mitochondria: Insights from Mechanistic and Evol...
Introduction
The Mitochondrial Hsp70 - Client Polypeptide Binding Cycle
Mdj1: Multifunctional JDP that Evolved Mitochondria-Specific Functions
Pam18: Specialized JDP that Functions in Protein Import
Hsc20: Specialized JDP that Functions in Iron-Sulfur Cluster Biogenesis
Evolutionary Dynamics of Mitochondrial JDP/Hsp70 Systems
Concluding Remarks
References
Chapter 11: Impact of Co-chaperones and Posttranslational Modifications Toward Hsp90 Drug Sensitivity
Introduction
The Chaperone Cycle
Canonical Co-chaperones
Hsp70/Hsp90-Organizing Protein (HOP)
Cell Division Cycle 37 (Cdc37)
Protein Phosphatase 5 (PP5)
Activator of Hsp90 ATPase 1 (Aha1)
Prostaglandin E Synthase 3 (p23)
Immunophilins
SGTA
Sgt1
C-Terminus of Hsc70-Interacting Protein (CHIP)
New Co-chaperones
Folliculin-Interacting Proteins 1 and 2 (FNIP1/2)
Tuberous Sclerosis Complex 1 (Tsc1)
TIMP-2
Concluding Remarks
References
Chapter 12: CHIP: A Co-chaperone for Degradation by the Proteasome and Lysosome
Introduction to Molecular Chaperones and Protein Degradation
Protein Degradation via the Proteasome
Protein Degradation via Autophagy and the Lysosome
The Carboxyl Terminus of Hsp70-Interacting Protein (CHIP)
Structure of CHIP
Interaction of CHIP with Chaperones and E2 Ligases
CHIP Substrates and Human Disease
Hsp70 and Hsp90: To Degrade or to Refold?
Conclusions
References
Chapter 13: HSP70-HSP90 Chaperone Networking in Protein-Misfolding Disease
Introduction
The HSP70 Chaperone Machine
The HSP90 Chaperone Machine
Major Co-chaperones Involved in Both HSP90 and HSP70 Complexes
Disruption of Proteostasis and Disease
Cooperation of HSP70 and HSP90 Chaperone Machines and Maintenance of Proteostasis in Neurodegenerative Disease
Conclusions
References
Index
