A litmus test for classifying recognition mechanisms of transiently binding proteins

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dc.citation.articleNumber3792en_US
dc.citation.journalTitleNature Communicationsen_US
dc.citation.volumeNumber13en_US
dc.contributor.authorChakrabarti, Kalyan S.en_US
dc.contributor.authorOlsson, Simonen_US
dc.contributor.authorPratihar, Supriyaen_US
dc.contributor.authorGiller, Karinen_US
dc.contributor.authorOverkamp, Kerstinen_US
dc.contributor.authorLee, Ko Onen_US
dc.contributor.authorGapsys, Vytautasen_US
dc.contributor.authorRyu, Kyoung-Seoken_US
dc.contributor.authorde Groot, Bert L.en_US
dc.contributor.authorNoé, Franken_US
dc.contributor.authorBecker, Stefanen_US
dc.contributor.authorLee, Donghanen_US
dc.contributor.authorWeikl, Thomas R.en_US
dc.contributor.authorGriesinger, Christianen_US
dc.date.accessioned2022-08-04T14:53:27Zen_US
dc.date.available2022-08-04T14:53:27Zen_US
dc.date.issued2022en_US
dc.description.abstractPartner recognition in protein binding is critical for all biological functions, and yet, delineating its mechanism is challenging, especially when recognition happens within microseconds. We present a theoretical and experimental framework based on straight-forward nuclear magnetic resonance relaxation dispersion measurements to investigate protein binding mechanisms on sub-millisecond timescales, which are beyond the reach of standard rapid-mixing experiments. This framework predicts that conformational selection prevails on ubiquitin’s paradigmatic interaction with an SH3 (Src-homology 3) domain. By contrast, the SH3 domain recognizes ubiquitin in a two-state binding process. Subsequent molecular dynamics simulations and Markov state modeling reveal that the ubiquitin conformation selected for binding exhibits a characteristically extended C-terminus. Our framework is robust and expandable for implementation in other binding scenarios with the potential to show that conformational selection might be the design principle of the hubs in protein interaction networks.en_US
dc.identifier.citationChakrabarti, Kalyan S., Olsson, Simon, Pratihar, Supriya, et al.. "A litmus test for classifying recognition mechanisms of transiently binding proteins." <i>Nature Communications,</i> 13, (2022) Springer Nature: https://doi.org/10.1038/s41467-022-31374-5.en_US
dc.identifier.digitals41467-022-31374-5en_US
dc.identifier.doihttps://doi.org/10.1038/s41467-022-31374-5en_US
dc.identifier.urihttps://hdl.handle.net/1911/112983en_US
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.rightsThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleA litmus test for classifying recognition mechanisms of transiently binding proteinsen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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