An Early Association between the α-Helix of the TEAD Binding Domain of YAP and TEAD Drives the Formation of the YAP:TEAD Complex

Bokhovchuk, Fedir; Mesrouze, Yannick; Meyerhofer, Marco; Zimmermann, Catherine; Fontana, Patrizia; Erdmann, Dirk; Jemth, Per; Chêne, Patrick

doi:10.1021/acs.biochem.0c00217

Cited by 18 publications

(30 citation statements)

References 47 publications

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“…The Cambrian-like NCBD/CID shows therefore an intermediate behavior between nucleationcondensation and diffusion-collision mechanism, that shifted towards nucleationcondensation during evolution. A similar diffusion-collision-like mechanism was recently found in the interaction between disordered YAP and TEAD (60). However, three other IDP interactions with more than one helical segment, Hif-1a CAD (58), TAD-STAT2 (57), and pKID (61) (all binding to KIX), do not display this behavior, but show mainly low f-values (<0.2) with only one or a few higher ones.…”

Section: Discussionsupporting

confidence: 69%

Mapping the transition state for a binding reaction between ancient intrinsically disordered proteins

Karlsson

Paissoni

Erkelens

et al. 2020

Journal of Biological Chemistry

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Intrinsically disordered protein domains often have multiple binding partners. It is plausible that the strength of pairing with specific partners evolves from an initial low to higher affinity. However, little is known about the molecular changes in the binding mechanism that would facilitate such a transition. We previously showed that the interaction between two intrinsically disordered domains, NCBD and CID, likely emerged in an ancestral deuterostome organism as a low-affinity interaction that subsequently evolved into a higher-affinity interaction before the radiation of modern vertebrate groups. Here we map native contacts in the transition states of the low-affinity ancestral and high-affinity human NCBD/CID interactions. We show that the coupled binding and folding mechanism is overall similar, but with a higher degree of native hydrophobic contact formation in the transition state of the ancestral complex and more heterogeneous transient interactions, including electrostatic pairings, and an increased disorder for the human complex. Adaptation to new binding partners may be facilitated by this ability to exploit multiple alternative transient interactions while retaining the overall binding and folding pathway.

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Section: Discussionsupporting

confidence: 69%

Mapping the transition state for a binding reaction between ancient intrinsically disordered proteins

Karlsson

Paissoni

Erkelens

et al. 2020

Journal of Biological Chemistry

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“…Pro85 Hs is important for maintaining the local structure at the N‐terminus of the Ω‐loop 22,24 . Pro92 Hs is probably required for the appropriate folding of the Ω‐loop and its mutation to alanine destabilizes the YAP:TEAD interaction by more than 3 kcal/mol 29 . The role of Pro99 Hs in the formation of the YAP:TEAD complex is unclear and its mutation to alanine has only a moderate effect on binding 24 .…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, the TBD of YAP forms a kind of dipole with its two binding sites harboring opposite charges. Ionic strength has a mild effect on the YAP: TEAD interaction, 29 so this spatial distribution of charges could be relevant for other aspects of YAP function, for example, to adopt specific conformations in solution.…”

Section: Sequence Analysis Of the Teadbinding Domain Of The Yap Promentioning

confidence: 99%

“…22,24 Pro92 Hs is probably required for the appropriate folding of the Ω-loop and its mutation to alanine destabilizes the YAP: TEAD interaction by more than 3 kcal/mol. 29 The role of Pro99 Hs in the formation of the YAP:TEAD complex is F I G U R E 2 Protein logos of the α-helix and Ω-loop regions of the TEAD-binding domain of YAP. The amino acid sequences of the TBD of YAP from Chordata, Arthropoda and "other phyla" (see text) species have been aligned.…”

Section: Sequence Analysis Of the Teadbinding Domain Of The Yap Promentioning

confidence: 99%

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Study of the TEAD‐binding domain of the YAP protein from animal species

et al. 2020

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The Hippo signaling pathway, which plays a central role in the control of organ size in animals, is well conserved in metazoans. The most downstream elements of this pathway are the TEAD transcription factors that are regulated by their association with the transcriptional coactivator YAP. Therefore, the creation of the binding interface that ensures the formation of the YAP:TEAD complex is a critical molecular recognition event essential for the development/survival of many living organisms. In this report, using the available structural information on the YAP:TEAD complex, we study the TEADbinding domain of YAP from different animal species. This analysis of more than 400 amino acid sequences reveals that the residues from YAP involved in the formation of the two main contact regions with TEAD are very well conserved. Therefore, the binding interface between YAP and TEAD, as found in humans, probably appeared at an early evolutionary stage in metazoans. We find that, in contrast to most other animal species, several Actinopterygii species possess YAP variants with a different TEAD-binding domain. However, these variants bind to TEAD with a similar affinity. Our studies show that the protein identified as a YAP homolog in Caenorhabditis elegans does not contain the TEAD-binding domain found in YAP of other metazoans. Finally, we do not identify in non-metazoan species, amino acid sequences containing both a TEAD-binding domain, as in metazoan YAP, and WW domain(s).

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“…All data points in the LFER plot exhibited good linearity, suggesting that the binding reaction occurs through a major TS (Fersht, 2004). In contrast, when binding occurs through highly distinct, multiple TSs, the LFER plot can show a non-linear relationship (Sánchez and Kiefhaber, 2003;Bokhovchuk et al, 2020). The Leffler α-value of the 1918 NS1:p85β interaction was measured to be 0.67 ± 0.06 (Figure 5A), indicating that the binding TS is located at a relatively later stage in the reaction coordinate.…”

Section: Characterization Of the Binding Transition Statementioning

confidence: 97%

Understanding the Binding Transition State After the Conformational Selection Step: The Second Half of the Molecular Recognition Process Between NS1 of the 1918 Influenza Virus and Host p85β

Dubrow

Kim

Topo

et al. 2021

Front. Mol. Biosci.

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Biomolecular recognition often involves conformational changes as a prerequisite for binding (i.e., conformational selection) or concurrently with binding (i.e., induced-fit). Recent advances in structural and kinetic approaches have enabled the detailed characterization of protein motions at atomic resolution. However, to fully understand the role of the conformational dynamics in molecular recognition, studies on the binding transition state are needed. Here, we investigate the binding transition state between nonstructural protein 1 (NS1) of the pandemic 1918 influenza A virus and the human p85β subunit of PI3K. 1918 NS1 binds to p85β via conformational selection. We present the free-energy mapping of the transition and bound states of the 1918 NS1:p85β interaction using linear free energy relationship and ϕ-value analyses. We find that the binding transition state of 1918 NS1 and p85β is structurally similar to the bound state with well-defined binding orientation and hydrophobic interactions. Our finding provides a detailed view of how protein motion contributes to the development of intermolecular interactions along the binding reaction coordinate.

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An Early Association between the α-Helix of the TEAD Binding Domain of YAP and TEAD Drives the Formation of the YAP:TEAD Complex

Cited by 18 publications

References 47 publications

Mapping the transition state for a binding reaction between ancient intrinsically disordered proteins

Mapping the transition state for a binding reaction between ancient intrinsically disordered proteins

Study of the TEAD‐binding domain of the YAP protein from animal species

Understanding the Binding Transition State After the Conformational Selection Step: The Second Half of the Molecular Recognition Process Between NS1 of the 1918 Influenza Virus and Host p85β

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