Conformational Selection in Substrate Recognition by Hsp70 Chaperones
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- 作者：Moritz Marcinowski1 ; 2 ; 1 ; Mathias Rosam1 ; 2 ; Christine Seitz2 ; 3 ; Johannes Elferich2 ; 3 ; Julia Behnke1 ; 2 ; 1 ; Claudia Bello1 ; 2 ; 1 ; Matthias J. Feige1 ; 2 ; 1 ; Christian F.W. Becker1 ; 2 ; 1 ; Iris Antes2 ; 3 ; antes@wzw.tum.de ; Johannes Buchner1 ; 2 ; johannes.buchner@tum.de
- 关键词：SBD ; substrate binding domain ; ER ; endoplasmic reticulum ; HC ; heavy chain ; wt ; wild type ; PDB ; Protein Data Bank ; SEC ; size-exclusion chromatography
- 刊名：Journal of Molecular Biology
- 出版年：2013
- 出版时间：8 February, 2013
- 年：2013
- 卷：425
- 期：3
- 页码：466-474
- 全文大小：847 K
文摘
Hsp70s are molecular chaperones involved in the folding and assembly of proteins. They recognize hydrophobic amino acid stretches in their substrate binding groove. However, a detailed understanding of substrate specificity is still missing. Here, we use the endoplasmic reticulum-resident Hsp70 BiP to identify binding sites in a natural client protein. Two sites are mutually recognized and form stable Hsp70-substrate complexes. In silico and in vitro analyses revealed an extended substrate conformation as a crucial factor for interaction and show an unexpected plasticity of the substrate binding groove. The basic binding mechanism is conserved among different Hsp70s.