TY  - JOUR
A1  - Morgner, Nina
A1  - Schmidt, Carla
A1  - Beilsten-Edmands, Victoria
A1  - Ebong, Ima-obong
A1  - Patel, Nisha A.
A1  - Clerico, Eugenia M.
A1  - Kirschke, Elaine
A1  - Daturpalli, Soumya
A1  - Jackson, Sophie E.
A1  - Agard, David
A1  - Robinson, Carol V.
T1  - Hsp70 forms antiparallel dimers stabilized by post-translational modifications to position clients for transfer to Hsp90
T2  - Cell reports
N2  - Protein folding in cells is regulated by networks of chaperones, including the heat shock protein 70 (Hsp70) system, which consists of the Hsp40 cochaperone and a nucleotide exchange factor. Hsp40 mediates complex formation between Hsp70 and client proteins prior to interaction with Hsp90. We used mass spectrometry (MS) to monitor assemblies formed between eukaryotic Hsp90/Hsp70/Hsp40, Hop, p23, and a client protein, a fragment of the glucocorticoid receptor (GR). We found that Hsp40 promotes interactions between the client and Hsp70, and facilitates dimerization of monomeric Hsp70. This dimerization is antiparallel, stabilized by post-translational modifications (PTMs), and maintained in the stable heterohexameric client-loading complex Hsp902Hsp702HopGR identified here. Addition of p23 to this client-loading complex induces transfer of GR onto Hsp90 and leads to expulsion of Hop and Hsp70. Based on these results, we propose that Hsp70 antiparallel dimerization, stabilized by PTMs, positions the client for transfer from Hsp70 to Hsp90.
Y1  - 2015
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/39425
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-394256
SN  - 2211-1247
N1  - This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
VL  - 11
IS  - 5
SP  - 759
EP  - 769
PB  - Cell Press
CY  - Maryland Heights, MO
ER  -