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Multiple WW domains of Nedd4‐1 undergo conformational exchange that is quenched upon peptide binding
Author(s) -
Panwalkar Vineet,
Neudecker Philipp,
Willbold Dieter,
Dingley Andrew J.
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12664
Subject(s) - ww domain , chemistry , affinities , peptide , biophysics , plasma protein binding , ubiquitin ligase , nedd4 , folding (dsp implementation) , context (archaeology) , stereochemistry , ubiquitin , biochemistry , biology , gene , paleontology , electrical engineering , engineering
The third WW domain ( WW 3*) of the ubiquitin ligase human neuronal precursor cell expressed developmentally downregulated gene 4‐1 ( hN edd4‐1) 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 hN edd4‐1 domains. In this report, NMR data show that the WW 3* 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 hN edd4‐1 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.