000069664 001__ 69664
000069664 005__ 20180410125951.0
000069664 0247_ $$2doi$$a10.18632/oncotarget.23909
000069664 0248_ $$2sideral$$a104644
000069664 037__ $$aART-2018-104644
000069664 041__ $$aeng
000069664 100__ $$aVerma, A.
000069664 245__ $$aBiophysical studies and NMR structure of YAP2 WW domain-LATS1 PPxY motif complexes reveal the basis of their interaction
000069664 260__ $$c2018
000069664 5060_ $$aAccess copy available to the general public$$fUnrestricted
000069664 5203_ $$aYES-associated protein (YAP) is a major effector protein of the Hippo tumor suppressor pathway, and is phosphorylated by the serine/threonine kinase LATS. Their binding is mediated by the interaction between WW domains of YAP and PPxY motifs of LATS. Their isoforms, YAP2 and LATS1 contain two WW domains and two PPxY motifs respectively. Here, we report the study of the interaction of these domains both in vitro and in human cell lines, to better understand the mechanism of their binding. We show that there is a reciprocal binding preference of YAP2-WW1 with LATS1-PPxY2, and YAP2-WW2 with LATS1-PPxY1. We solved the NMR structures of these complexes and identified several conserved residues that play a critical role in binding. We further created a YAP2 mutant by swapping the WW domains, and found that YAP2 phosphorylation at S127 by LATS1 is not affected by the spatial configuration of its WW domains. This is likely because the region between the PPxY motifs of LATS1 is unstructured, even upon binding with its partner. Based on our observations, we propose possible models for the interaction between YAP2 and LATS1.
000069664 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000069664 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000069664 700__ $$aJing-Song, F.
000069664 700__ $$aFinch-Edmondson, M.L.
000069664 700__ $$0(orcid)0000-0001-5702-4538$$aVelazquez-Campoy, A.$$uUniversidad de Zaragoza
000069664 700__ $$aBalasegaran, S.
000069664 700__ $$aSudol, M.
000069664 700__ $$aSivaraman, J.
000069664 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDepartamento de Bioquímica y Biología Molecular y Celular$$cBioquímica y Biología Molecular
000069664 773__ $$g9, 8 (2018), 8068-8080$$pONCOTARGET$$tONCOTARGET$$x1949-2553
000069664 8564_ $$s1011060$$uhttp://zaguan.unizar.es/record/69664/files/texto_completo.pdf$$yVersión publicada
000069664 8564_ $$s124664$$uhttp://zaguan.unizar.es/record/69664/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000069664 909CO $$ooai:zaguan.unizar.es:69664$$particulos$$pdriver
000069664 951__ $$a2018-04-10-12:16:27
000069664 980__ $$aARTICLE