32DH
Crystal structure of YAP1(165-209) in complex with LATS2(511-522_C513S)
Summary for 32DH
| Entry DOI | 10.2210/pdb32dh/pdb |
| Descriptor | Transcriptional coactivator YAP1, Serine/threonine-protein kinase LATS2 (3 entities in total) |
| Functional Keywords | yap1, transcriptional co-activator, yes-associated protein 1, protein yorkie homolog, yes-associated protein yap65 homolog, lats2, large tumor suppressor homolog 2, protein complex, transcription |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 7003.93 |
| Authors | |
| Primary citation | Merlen, C.,Mesrouze, Y.,Chau, S.,Diehl, B.A.,Hinniger, A.,Zimmermann, C.,Meyerhofer, M.,Fontana, P.,Groebke, S.,Hinrichs, J.,Abdul Rahman, W.,Gutmann, S.,Fernandez, C.,Petrovic, D.,Chene, P. Comparing YAP WW1 and TAZ WW : Similar Binding Sites but Different Stability and Conformational Dynamics. Biomolecules, 16:-, 2026 Cited by PubMed Abstract: The two paralogs YAP and TAZ act through TEAD transcription factors and bind PPxY motif proteins in the Hippo pathway via WW domains. YAP has up to two WW domains, whereas TAZ has one. Because YAP and TAZ are the most similar in sequence, they can be considered as corresponding modules in these two proteins. This study shows that, despite their similarity, they differ strongly in conformational stability and in how they bind flexible ligands. Nano-differential scanning fluorimetry, circular dichroism, and NMR indicate that both isolated domains populate partially folded or exchanging states in solution, but TAZ is more thermally stable and has a larger folded population. Peptide binding stabilizes both domains, producing sharper NMR signals. Surface plasmon resonance measurements with PPxY peptides show micromolar affinities and generally modest differences between YAP and TAZ, although these differences increase for conformationally plastic ligands. A high resolution LATS2:YAP crystal structure and molecular dynamics simulations suggest that preorganized peptides bind more tightly and less selectively, while flexible peptides incur larger binding penalties that dynamic YAP compensates more effectively. These observations indicate that differences in WW-domain stability contribute to subtle YAP/TAZ binding preferences despite conserved binding surfaces and evolutionary relatedness between the paralogs. PubMed: 42793187DOI: 10.3390/biom16091355 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.03 Å) |
Structure validation
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