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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/26446

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
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
URI: http://hdl.handle.net/1942/26446
DOI: 10.1038/s41594-017-0012-6
ISI #: 000423547700013
ISSN: 1545-9993
Category: A1
Type: Journal Contribution
Appears in Collections: Research publications

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