%0 Journal Article
%A Panwalkar, Vineet
%A Neudecker, Philipp
%A Willbold, Dieter
%A Dingley, Andrew J.
%T Multiple WW domains of Nedd4-1 undergo conformational exchange that is quenched upon peptide binding
%J FEBS letters
%V 591
%N 11
%@ 0014-5793
%C Chichester
%I Wiley
%M FZJ-2018-06835
%P 1573 - 1583
%D 2017
%X The third WW domain (WW3*) of the ubiquitin ligase human neuronal precursor cell expressed developmentally downregulated gene 4-1 (hNedd4-1) was reported to bind its PY motif peptide by a coupled folding-binding equilibrium. However, it is unknown whether these thermodynamic properties are retained in the context of neighboring hNedd4-1 domains. In this report, NMR data show that the WW3* displays a fold-unfold equilibrium in the presence of neighboring WW domains, and that similar fold-unfold equilibria also likely exist for neighboring WW domains. These equilibria are quenched upon interaction with peptide. Thus, the binding mechanism of hNedd4-1 WW domains to proteins involves coupled folding and binding equilibria, and this mechanism may be a general feature that modulates peptide affinities of WW domains.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:28471472
%U <Go to ISI:>//WOS:000403354400009
%R 10.1002/1873-3468.12664
%U https://juser.fz-juelich.de/record/857872