Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/144260
Title: BIOPHYSICAL STUDIES TO ELUCIDATE THE RECOGNITION MECHANISM OF HIPPO PATHWAY EFFECTORS YAP AND TAZ BY LATS1
Authors: APOORVA VERMA
Keywords: Hippo pathway, YAP, TAZ, LATS, WW domain, PPxY motif
Issue Date: 25-Aug-2017
Citation: APOORVA VERMA (2017-08-25). BIOPHYSICAL STUDIES TO ELUCIDATE THE RECOGNITION MECHANISM OF HIPPO PATHWAY EFFECTORS YAP AND TAZ BY LATS1. ScholarBank@NUS Repository.
Abstract: The Hippo pathway is a regulator of cell proliferation and apoptosis. YAP and TAZ are the effectors of the pathway, and are phosphorylated by the serine/threonine kinase LATS. The binding is mediated by the interaction between WW domain(s) of YAP/TAZ and PPxY motif(s) of LATS1. We show that there is a reciprocal binding preference of YAP2-WW1 with LATS1-PPxY2, and YAP2-WW2 with LATS1-PPxY1 in vitro. We solved the NMR structures of these complexes, and identified the binding site residues. We showed that YAP2 phosphorylation at S127 by LATS1 is not affected by the spatial configuration of its WW domains. We further propose possible models for the interaction between YAP2 and LATS1. TAZ, the other hand, contains only a single WW domain that also prefers the second PPxY motif of LATS1. We modelled the structure of their complex, and performed MD simulations to show the complex is stable. We mutated the binding site residues to assess their contribution towards the binding.
URI: http://scholarbank.nus.edu.sg/handle/10635/144260
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