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http://hdl.handle.net/1942/26446
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DC Field | Value | Language |
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dc.contributor.author | Rosam, Mathias | - |
dc.contributor.author | Krader, Daniela | - |
dc.contributor.author | Nickels, Christina | - |
dc.contributor.author | Hochmair, Janine | - |
dc.contributor.author | Back, Katrin C. | - |
dc.contributor.author | Agam, Ganesh | - |
dc.contributor.author | Barth, Anders | - |
dc.contributor.author | Zeymer, Cathleen | - |
dc.contributor.author | HENDRIX, Jelle | - |
dc.contributor.author | Schneider, Markus | - |
dc.contributor.author | Antes, Iris | - |
dc.contributor.author | Reinstein, Jochen | - |
dc.contributor.author | Lamb, Don C. | - |
dc.contributor.author | Buchner, Johannes | - |
dc.date.accessioned | 2018-07-27T13:47:52Z | - |
dc.date.available | 2018-07-27T13:47:52Z | - |
dc.date.issued | 2018 | - |
dc.identifier.citation | NATURE STRUCTURAL & MOLECULAR BIOLOGY, 25(1), p. 90-100 | - |
dc.identifier.issn | 1545-9993 | - |
dc.identifier.uri | http://hdl.handle.net/1942/26446 | - |
dc.description.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. | - |
dc.description.sponsorship | We thank J. Lawatschek and K. Richter for help with experiments, L. Voith von Voithenberg for helpful and critical discussions regarding spFRET experiments as well as data analysis, W. Kugel for contributions to the spFRET analysis software, G. M. Feind for performing the HDX analysis and K. Buhr for help with the structural modeling of the BiP-peptide complexes. We gratefully acknowledge the financial support by the Deutsche Forschungsgemeinschaft to J.B. (DFG), D.C.L. (SFB1035, A11), I. A. (SFB1035, A10) and M.S. (IGSSE) and by the Ludwig-Maximilians-Universitat through the Center for NanoScience (CeNS) and the BioImaging Network (BIN). | - |
dc.language.iso | en | - |
dc.rights | © 2017 Nature America Inc., part of Springer Nature. All rights reserved. | - |
dc.title | Bap (Sil1) regulates the molecular chaperone BiP by coupling release of nucleotide and substrate | - |
dc.type | Journal Contribution | - |
dc.identifier.epage | 100 | - |
dc.identifier.issue | 1 | - |
dc.identifier.spage | 90 | - |
dc.identifier.volume | 25 | - |
local.bibliographicCitation.jcat | A1 | - |
dc.description.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 | - |
local.type.refereed | Refereed | - |
local.type.specified | Article | - |
dc.identifier.doi | 10.1038/s41594-017-0012-6 | - |
dc.identifier.isi | 000423547700013 | - |
item.fullcitation | 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 (2018) Bap (Sil1) regulates the molecular chaperone BiP by coupling release of nucleotide and substrate. In: NATURE STRUCTURAL & MOLECULAR BIOLOGY, 25(1), p. 90-100. | - |
item.validation | ecoom 2019 | - |
item.accessRights | Restricted Access | - |
item.fulltext | With Fulltext | - |
item.contributor | Rosam, Mathias | - |
item.contributor | Krader, Daniela | - |
item.contributor | Nickels, Christina | - |
item.contributor | Hochmair, Janine | - |
item.contributor | Back, Katrin C. | - |
item.contributor | Agam, Ganesh | - |
item.contributor | Barth, Anders | - |
item.contributor | Zeymer, Cathleen | - |
item.contributor | HENDRIX, Jelle | - |
item.contributor | Schneider, Markus | - |
item.contributor | Antes, Iris | - |
item.contributor | Reinstein, Jochen | - |
item.contributor | Lamb, Don C. | - |
item.contributor | Buchner, Johannes | - |
crisitem.journal.issn | 1545-9993 | - |
crisitem.journal.eissn | 1545-9985 | - |
Appears in Collections: | Research publications |
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rosam2018.pdf Restricted Access | Published version | 2.67 MB | Adobe PDF | View/Open Request a copy |
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