Proteomics

Dataset Information

0

Effects of a phosphomimetic mutation and nucleotide binding on the interaction of Hsp90a with co-chaperone Aha1 analyzed by chemical cross-linking with mass spectrometry

ABSTRACT: Complex conformational dynamics are essential for the chaperone function of heat shock protein 90 (Hsp90), including transient, ATP-biased N-domain dimerization establishing ATPase competence. Biochemical data demonstrate that the intrinsic, but weak, ATP hydrolyzing activity of Hsp90 is markedly enhanced by the co-chaperone Aha1. However, cellular concentration of Aha1 is substoichiometric relative to Hsp90. In cells, interaction of this important co-chaperone with Hsp90 is up-regulated by posttranslational modifications (PTMs), including phosphorylation of a highly conserved tyrosine (Y313 in Hsp90a). Here we use chemical cross-linking with mass spectrometry to explore the the impacts of a phosphomimetic mutation (Y313E) and binding of a non-hydrolyzable ATP analog (AMP-PNP),on the structure Hsp90a and its interaction with Aha1.

INSTRUMENT(S): LTQ FT, Q Exactive

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Juan Chavez  

LAB HEAD: Len Neckers

PROVIDER: PXD013476 | Pride | 2019-06-17

REPOSITORIES: Pride

Json Xml
altmetric image

Publications

Hsp90 middle domain phosphorylation initiates a complex conformational program to recruit the ATPase-stimulating cochaperone Aha1.

Xu Wanping W   Beebe Kristin K   Chavez Juan D JD   Boysen Marta M   Lu YinYing Y   Zuehlke Abbey D AD   Keramisanou Dimitra D   Trepel Jane B JB   Prodromou Christosomos C   Mayer Matthias P MP   Bruce James E JE   Gelis Ioannis I   Neckers Len L  

Nature communications 20190612 1

Complex conformational dynamics are essential for function of the dimeric molecular chaperone heat shock protein 90 (Hsp90), including transient, ATP-biased N-domain dimerization that is necessary to attain ATPase competence. The intrinsic, but weak, ATP hydrolyzing activity of human Hsp90 is markedly enhanced by the co-chaperone Aha1. However, the cellular concentration of Aha1 is substoichiometric relative to Hsp90. Here we report that initial recruitment of this cochaperone to Hsp90 is marked  ...[more]

Similar Datasets

Proteomics c-Abl Dependent Tyrosine Phosphorylation of theCo-chaperone Aha1 Regulates Interaction with Hsp90
2017-03-28 | MSV000080713 | MassIVE
Proteomics c-Abl Dependent Tyrosine Phosphorylation of theCo-chaperone Aha1 Regulates Interaction with Hsp90
2015-08-06 | PXD001737 | Pride
Proteomics The Hsp90 molecular chaperone governs client proteins by targeting intrinsically disordered regions
2023-08-10 | PXD040875 | Pride
Proteomics Proximity Proteomics Revealed Dicer1 and Transporters as Client Proteins of Aha1
2022-11-19 | PXD028980 | Pride
Proteomics The IMiD receptor CRBN determines quality control of transmembrane proteins
2021-02-18 | PXD018244 | Pride
Genomics Heat-shock protein 90 globally targets paused promoters and regulates environment-induced gene expression
2012-05-14 | E-GEOD-31226 | biostudies-arrayexpress
Proteomics Hsp multichaperone complex buffers pathologically modified Tau
2022-08-11 | PXD032037 | Pride
Proteomics Cellular interactome dynamics during paclitaxel treatment
2019-11-21 | PXD015751 | Pride
Proteomics Translational reprogramming in response to accumulating stressors ensures critical threshold levels of Hsp90 for mammalian life
2022-09-20 | PXD031456 | Pride
Proteomics Characterizations of HSP90-interacting complex in renal cells using tandem affinity purification and its potential role in kidney stone formation
2018-12-17 | PXD011432 | Pride