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Bomblies, R.* ; Luitz, M.P.* ; Scanu, S.* ; Madl, T. ; Zacharias, M.*

Transient helicity in intrinsically disordered Axin-1 studied by NMR spectroscopy and molecular dynamics simulations.

PLoS ONE 12:e0174337 (2017)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Many natural proteins are, as a whole or in part, intrinsically disordered. Frequently, such intrinsically disordered regions (IDRs) undergo a transition to a defined and often helical conformation upon binding to partner molecules. The intrinsic propensity of an IDR sequence to fold into a helical conformation already in the absence of a binding partner can have a decisive influence on the binding process and affinity. Using a combination of NMR spectroscopy and molecular dynamics (MD) simulations we have investigated the tendency of regions of Axin-1, an intrinsically disordered scaffolding protein of the WNT signaling pathway, to form helices in segments interacting with binding partners. Secondary chemical shifts from NMR measurements show an increased helical population in these regions. Systematic application of MD advanced sampling approaches on peptide segments of Axin-1 reproduces the experimentally observed tendency and allows insights into the distribution of segment conformations and free energies of helix formation. The results, however, were found to dependent on the force field water model. Recent water models specifically designed for IDRs significantly reduce the predicted helical content and do not improve the agreement with experiment.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Beta-catenin; Unstructured Proteins; Structural Basis; Human-diseases; Force-fields; Association; Water; Ensembles; Pathway; Regions
ISSN (print) / ISBN 1932-6203
Zeitschrift PLoS ONE
Quellenangaben Band: 12, Heft: 3, Seiten: , Artikelnummer: e0174337 Supplement: ,
Verlag Public Library of Science (PLoS)
Verlagsort Lawrence, Kan.
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Structural Biology (STB)