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|Title: ||Bap (Sil1) regulates the molecular chaperone BiP by coupling release of nucleotide and substrate|
|Authors: ||Rosam, Mathias|
Back, Katrin C.
Lamb, Don C.
|Issue Date: ||2018|
|Citation: ||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. email@example.com; firstname.lastname@example.org|
|ISI #: ||000423547700013|
|Type: ||Journal Contribution|
|Appears in Collections: ||Research publications|
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