Hsp70-Substrate Interactions

  • Roman Kityk
  • Matthias P. Mayer


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.


Chaperones Hsp70 Hsp90 Protein folding Protein degradation Protein-protein interactions Quality control Stress response 



Endoplasmic reticulum


Heat shock protein


J-domain protein, also called DnaJ proteins or Hsp40


Nucleotide-binding domain


Nucleotide exchange factor


Substrate-binding domain


α-Helical lid subdomain of the SBD


β-Sandwich subdomain of the SBD


Unfolded protein response


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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

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

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