文章基本信息

标题：Long-range structural preformation in yes-associated protein precedes encounter complex formation with TEAD
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作者：Michael Feichtinger ; Andreas Beier ; Mario Migotti 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：4
页码：1-17
DOI：10.1016/j.isci.2022.104099
语种：English
出版社：Elsevier
摘要：SummaryYes-associated protein (YAP) is a partly intrinsically disordered protein (IDP) that plays a major role as the downstream element of the Hippo pathway. Although the structures of the complex between TEA domain transcription factors (TEADs) and the TEAD-binding domain of YAP are already well characterized, its apo state and the binding mechanism with TEADs are still not clearly defined. Here we characterize via a combination of different NMR approaches with site-directed mutagenesis and affinity measurements the intrinsically disordered solution state of apo YAP. Our results provide evidence that the apo state of YAP adopts several compact conformations that may facilitate the formation of the YAP:TEAD complex. The interplay between local secondary structure element preformation and long-range co-stabilization of these structured elements precedes the encounter complex formation with TEAD and we, therefore, propose that TEAD binding proceeds largely via conformational selection of the preformed compact substates displaying at least nanosecond lifetimes.Graphical abstractDisplay OmittedHighlights•Secondary structure elements are preformed in apo YAP•Preformation of secondary structure elements is co-dependent•Apo YAP exhibits long-range structural compaction•YAP compaction has a kinetic contribution to the YAP:TEAD formationBiochemistry; Cell biology; Structural biology