8A8Q

Crystal structure of Protein Scalloped in complex with YAP peptide

Summary for 8A8Q

• Entry DOI: 10.2210/pdb8a8q/pdb
• Descriptor: Protein scalloped, Isoform 7 of Transcriptional coactivator YAP1, ACETATE ION, ... (4 entities in total)
• Functional Keywords: complex, transcription
• Biological source: Drosophila melanogaster (fruit fly); More
• Total number of polymer chains: 4
• Total formula weight: 62625.69

Authors

Scheufler, C.,Villard, F. (deposition date: 2022-06-23, release date: 2022-12-28, Last modification date: 2024-05-01)

Primary citation

Fedir, B.,Yannick, M.,Marco, M.,Patrizia, F.,Catherine, Z.,Frederic, V.,Dirk, E.,Joerg, K.,Clemens, S.,Camilo, V.V.,Patrick, C.
N-terminal beta-strand in YAP is critical for stronger binding to scalloped relative to TEAD transcription factor.
Protein Sci., 32:e4545-e4545, 2023

PubMed Abstract: The yes-associated protein (YAP) regulates the transcriptional activity of the TEAD transcription factors that are key in the control of organ morphogenesis. YAP interacts with TEAD via three secondary structure elements: a β-strand, an α-helix, and an Ω-loop. Earlier results have shown that the β-strand has only a marginal contribution in the YAP:TEAD interaction, but we show here that it significantly enhances the affinity of YAP for the Drosophila homolog of TEAD, scalloped (Sd). Nuclear magnetic resonance shows that the β-strand adopts a more rigid conformation once bound to Sd; pre-steady state kinetic measurements show that the YAP:Sd complex is more stable. Although the crystal structures of the YAP:TEAD and YAP:Sd complexes reveal no differences at the binding interface that could explain these results. Molecular Dynamics simulations are in line with our experimental findings regarding β-strand stability and overall binding affinity of YAP to TEAD and Sd. In particular, RMSF, correlated motion and MMGBSA analyses suggest that β-sheet fluctuations play a relevant role in YAP β-strand dissociation from TEAD4 and contribute to the lower affinity of YAP for TEAD4. Identifying a clear mechanism leading to the difference in YAP's β-strand stability proved to be challenging, pointing to the potential relevance of multiple modest structural changes or fluctuations for regulation of binding affinity.

PubMed: 36522189
DOI: 10.1002/pro.4545

Experimental method

X-RAY DIFFRACTION (1.465 Å)