Tuning of chaperone activity of Hsp70 proteins by modulation of nucleotide exchange

Dirk Brehmer; Stefan Rüdiger; Claudia S. Gässler; Dagmar Klostermeier; Lars Packschies; Jochen Reinstein; Matthias P. Mayer; Bernd Bukau

doi:10.1038/87588

Tuning of chaperone activity of Hsp70 proteins by modulation of nucleotide exchange

Dirk Brehmer, Stefan Rüdiger, Claudia S. Gässler, Dagmar Klostermeier, Lars Packschies, Jochen Reinstein, Matthias P. Mayer, Bernd Bukau

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

The Hsp70 chaperone activity in protein folding is regulated by ATP-controlled cycles of substrate binding and release. Nucleotide exchange plays a key role in these cycles by triggering substrate release. Structural searches of Hsp70 homologs revealed three structural elements within the ATPase domain: two salt bridges and an exposed loop. Mutational analysis showed that these elements control the dissociation of nucleotides, the interaction with exchange factors and chaperone activity. Sequence variations in the three elements classify the Hsp70 family members into three subfamilies, DnaK proteins, HscA proteins and Hsc70 proteins. These subfamilies show strong differences in nucleotide dissociation and interaction with the exchange factors GrpE and Bag-1.

Original language	English
Pages (from-to)	427-432
Number of pages	6
Journal	Nature Structural Biology
Volume	8
Issue number	5
DOIs	https://doi.org/10.1038/87588
Publication status	Published - 9 Dec 2001
Externally published	Yes

Keywords

adenosine triphosphatase
chaperone
heat shock protein 70
nucleotide
protein DnaK
article
conformational transition
dissociation
molecular interaction
mutation
priority journal
protein domain
protein family
protein folding
sequence analysis

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title = "Tuning of chaperone activity of Hsp70 proteins by modulation of nucleotide exchange",

abstract = "The Hsp70 chaperone activity in protein folding is regulated by ATP-controlled cycles of substrate binding and release. Nucleotide exchange plays a key role in these cycles by triggering substrate release. Structural searches of Hsp70 homologs revealed three structural elements within the ATPase domain: two salt bridges and an exposed loop. Mutational analysis showed that these elements control the dissociation of nucleotides, the interaction with exchange factors and chaperone activity. Sequence variations in the three elements classify the Hsp70 family members into three subfamilies, DnaK proteins, HscA proteins and Hsc70 proteins. These subfamilies show strong differences in nucleotide dissociation and interaction with the exchange factors GrpE and Bag-1.",

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author = "Dirk Brehmer and Stefan R{\"u}diger and G{\"a}ssler, {Claudia S.} and Dagmar Klostermeier and Lars Packschies and Jochen Reinstein and Mayer, {Matthias P.} and Bernd Bukau",

year = "2001",

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doi = "10.1038/87588",

language = "English",

volume = "8",

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journal = "Nature Structural Biology",

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TY - JOUR

T1 - Tuning of chaperone activity of Hsp70 proteins by modulation of nucleotide exchange

AU - Brehmer, Dirk

AU - Rüdiger, Stefan

AU - Gässler, Claudia S.

AU - Klostermeier, Dagmar

AU - Packschies, Lars

AU - Reinstein, Jochen

AU - Mayer, Matthias P.

AU - Bukau, Bernd

PY - 2001/12/9

Y1 - 2001/12/9

N2 - The Hsp70 chaperone activity in protein folding is regulated by ATP-controlled cycles of substrate binding and release. Nucleotide exchange plays a key role in these cycles by triggering substrate release. Structural searches of Hsp70 homologs revealed three structural elements within the ATPase domain: two salt bridges and an exposed loop. Mutational analysis showed that these elements control the dissociation of nucleotides, the interaction with exchange factors and chaperone activity. Sequence variations in the three elements classify the Hsp70 family members into three subfamilies, DnaK proteins, HscA proteins and Hsc70 proteins. These subfamilies show strong differences in nucleotide dissociation and interaction with the exchange factors GrpE and Bag-1.

AB - The Hsp70 chaperone activity in protein folding is regulated by ATP-controlled cycles of substrate binding and release. Nucleotide exchange plays a key role in these cycles by triggering substrate release. Structural searches of Hsp70 homologs revealed three structural elements within the ATPase domain: two salt bridges and an exposed loop. Mutational analysis showed that these elements control the dissociation of nucleotides, the interaction with exchange factors and chaperone activity. Sequence variations in the three elements classify the Hsp70 family members into three subfamilies, DnaK proteins, HscA proteins and Hsc70 proteins. These subfamilies show strong differences in nucleotide dissociation and interaction with the exchange factors GrpE and Bag-1.

KW - adenosine triphosphatase

KW - chaperone

KW - heat shock protein 70

KW - nucleotide

KW - protein DnaK

KW - article

KW - conformational transition

KW - dissociation

KW - molecular interaction

KW - mutation

KW - priority journal

KW - protein domain

KW - protein family

KW - protein folding

KW - sequence analysis

U2 - 10.1038/87588

DO - 10.1038/87588

M3 - Article

SN - 1072-8368

VL - 8

SP - 427

EP - 432

JO - Nature Structural Biology

JF - Nature Structural Biology

IS - 5

ER -

Tuning of chaperone activity of Hsp70 proteins by modulation of nucleotide exchange

Abstract

Keywords

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