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dc.contributor.author
Zosel, Franziska
dc.contributor.author
Mercadante, Davide
dc.contributor.author
Nettels, Daniel
dc.contributor.author
Schuler, Benjamin
dc.date.accessioned
2019-01-23T14:33:10Z
dc.date.available
2019-01-23T08:22:35Z
dc.date.available
2019-01-23T14:33:10Z
dc.date.issued
2018-08-20
dc.identifier.issn
2041-1723
dc.identifier.other
10.1038/s41467-018-05725-0
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/318757
dc.identifier.doi
10.3929/ethz-b-000318757
dc.description.abstract
The interactions of intrinsically disordered proteins (IDPs) with their molecular targets are essential for the regulation of many cellular processes. IDPs can perform their functions while disordered, and they may fold to structured conformations on binding. Here we show that the cis/trans isomerization of peptidyl−prolyl bonds can have a pronounced effect on the interactions of IDPs. By single-molecule spectroscopy, we identify a conserved proline residue in NCBD (the nuclear-coactivator binding domain of CBP) whose cis/trans isomerization in the unbound state modulates the association and dissociation rates with its binding partner, ACTR. As a result, NCBD switches on a time scale of tens of seconds between two populations that differ in their affinities to ACTR by about an order of magnitude. Molecular dynamics simulations indicate as a cause reduced packing of the complex for the cis isomer. Peptidyl-prolyl cis/trans isomerization may be an important previously unidentified mechanism for regulating IDP interactions.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Nature
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Biophysical chemistry
en_US
dc.subject
Biophysics
en_US
dc.subject
Kinetics
en_US
dc.subject
Reaction kinetics and dynamics
en_US
dc.subject
Molecular biophysics
en_US
dc.title
A proline switch explains kinetic heterogeneity in a coupled folding and binding reaction
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
ethz.journal.title
Nature Communications
ethz.journal.volume
9
en_US
ethz.journal.abbreviated
Nat Commun
ethz.pages.start
3332
en_US
ethz.size
10 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.grant
Role of Disordered Regions in RNA-Binding Proteins for Function and Pathology
en_US
ethz.publication.place
London
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00003 - Schulleitung und Dienste::00022 - Bereich VP Forschung / Domain VP Research::02207 - Functional Genomics Center Zurich / Functional Genomics Center Zurich
en_US
ethz.grant.agreementno
170976
ethz.grant.fundername
SNF
ethz.grant.funderDoi
10.13039/501100001711
ethz.grant.program
Sinergia
ethz.date.deposited
2019-01-23T08:22:53Z
ethz.source
FORM
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2019-01-23T14:33:35Z
ethz.rosetta.lastUpdated
2024-02-02T07:01:50Z
ethz.rosetta.versionExported
true
ethz.COinS
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