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Hsp70-Substrate Interactions

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Heat Shock Proteins in the Immune System

Abstract

The highly abundant and evolutionary conserved Hsp70 chaperones are central components of the cellular protein quality control system, surveilling the folding status of cellular proteins from birth at the ribosome to death through degradation. To no other chaperone families, more different functions have been assigned, and it is not surprising that Hsp70s are implicated in many developmental processes and pathological conditions. This versatility is due to the fact that Hsp70s bind tweezer-like degenerate motifs present in virtually all proteins, generally found in the hydrophobic core of the native conformation but exposed in the nascent state at the ribosome or translocation pores or upon stress-induced denaturation and aggregation. Recent years have seen much progress in understanding the molecular mechanism of this chaperone family. In this chapter, we review the current knowledge on structure, different conformational states, allostery, and regulation by co-chaperones in the context of Hsp70-substrate interaction.

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Abbreviations

ER:

Endoplasmic reticulum

Hsp:

Heat shock protein

JDP:

J-domain protein, also called DnaJ proteins or Hsp40

NBD:

Nucleotide-binding domain

NEF:

Nucleotide exchange factor

SBD:

Substrate-binding domain

SBDα:

α-Helical lid subdomain of the SBD

SBDβ:

β-Sandwich subdomain of the SBD

UPR:

Unfolded protein response

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Authors and Affiliations

  1. Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH-Alliance, Heidelberg, Germany

    Roman Kityk & Matthias P. Mayer

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  1. Roman Kityk
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  2. Matthias P. Mayer
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Correspondence to Matthias P. Mayer .

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  1. Department of Immunology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania, USA

    Robert J. Binder

  2. Carole and Ray Neag Comprehensive Cancer Center and the Department of Immunology, University of Connecticut School of Medicine, Farmington, Connecticut, USA

    Pramod K. Srivastava

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Kityk, R., Mayer, M.P. (2018). Hsp70-Substrate Interactions. In: Binder, R., Srivastava, P. (eds) Heat Shock Proteins in the Immune System. Springer, Cham. https://doi.org/10.1007/978-3-319-69042-1_1

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