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Title: | Bap (Sil1) regulates the molecular chaperone BiP by coupling release of nucleotide and substrate | Authors: | Rosam, Mathias Krader, Daniela Nickels, Christina Hochmair, Janine Back, Katrin C. Agam, Ganesh Barth, Anders Zeymer, Cathleen HENDRIX, Jelle Schneider, Markus Antes, Iris Reinstein, Jochen Lamb, Don C. Buchner, Johannes |
Issue Date: | 2018 | Source: | NATURE STRUCTURAL & MOLECULAR BIOLOGY, 25(1), p. 90-100 | Abstract: | BiP is the endoplasmic member of the Hsp70 family. BiP is regulated by several co-chaperones including the nucleotide-exchange factor (NEF) Bap (Sil1 in yeast). Bap is a two-domain protein. The interaction of the Bap C-terminal domain with the BiP ATPase domain is sufficient for its weak NEF activity. However, stimulation of the BiP ATPase activity requires full-length Bap, suggesting a complex interplay of these two factors. Here, single-molecule FRET experiments with mammalian proteins reveal that Bap affects the conformation of both BiP domains, including the lid subdomain, which is important for substrate binding. The largely unstructured Bap N-terminal domain promotes the substrate release from BiP. Thus, Bap is a conformational regulator affecting both nucleotide and substrate interactions. The preferential interaction with BiP in its ADP state places Bap at a late stage of the chaperone cycle, in which it coordinates release of substrate and ADP, thereby resetting BiP for ATP and substrate binding. | Notes: | Buchner, J (reprint author), Tech Univ Munich, Ctr Integrated Prot Sci Munich, Dept Chem, Garching, Germany. d.lamb@lmu.de; johannes.buchner@tum.de | Document URI: | http://hdl.handle.net/1942/26446 | ISSN: | 1545-9993 | e-ISSN: | 1545-9985 | DOI: | 10.1038/s41594-017-0012-6 | ISI #: | 000423547700013 | Rights: | © 2017 Nature America Inc., part of Springer Nature. All rights reserved. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2019 |
Appears in Collections: | Research publications |
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