Atomistic fingerprint of hyaluronan-CD44 binding

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Vuorio , J , Vattulainen , I & Martinez-Seara , H 2017 , ' Atomistic fingerprint of hyaluronan-CD44 binding ' , PLoS Computational Biology , vol. 13 , no. 7 , 1005663 . https://doi.org/10.1371/journal.pcbi.1005663

Title: Atomistic fingerprint of hyaluronan-CD44 binding
Author: Vuorio, Joni; Vattulainen, Ilpo; Martinez-Seara, Hector
Contributor: University of Helsinki, Tampere University of Technology
University of Helsinki, Department of Physics
Date: 2017-07
Language: eng
Number of pages: 24
Belongs to series: PLoS Computational Biology
ISSN: 1553-734X
URI: http://hdl.handle.net/10138/217912
Abstract: Hyaluronan is a polyanionic, megadalton-scale polysaccharide, which initiates cell signaling by interacting with several receptor proteins including CD44 involved in cell-cell interactions and cell adhesion. Previous studies of the CD44 hyaluronan binding domain have identified multiple widespread residues to be responsible for its recognition capacity. In contrast, the X-ray structural characterization of CD44 has revealed a single binding mode associated with interactions that involve just a fraction of these residues. In this study, we show through atomistic molecular dynamics simulations that hyaluronan can bind CD44 with three topographically different binding modes that in unison define an interaction fingerprint, thus providing a plausible explanation for the disagreement between the earlier studies. Our results confirm that the known crystallographic mode is the strongest of the three binding modes. The other two modes represent metastable configurations that are readily available in the initial stages of the binding, and they are also the most frequently observed modes in our unbiased simulations. We further discuss how CD44, fostered by the weaker binding modes, diffuses along HA when attached. This 1D diffusion combined with the constrained relative orientation of the diffusing proteins is likely to influence the aggregation kinetics of CD44. Importantly, CD44 aggregation has been suggested to be a possible mechanism in CD44-mediated signaling.
Subject: MOLECULAR SIMULATIONS
PROTEIN-INTERACTION
N-GLYCOSYLATION
RECEPTOR CD44
FORCE-FIELD
DOMAIN
SITE
ADHESION
IDENTIFICATION
GLYCOCALYX
1182 Biochemistry, cell and molecular biology
114 Physical sciences
116 Chemical sciences
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