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Atomistic fingerprint of hyaluronan-CD44 binding
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SYSNO ASEP 0478304 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Atomistic fingerprint of hyaluronan-CD44 binding Author(s) Vuorio, J. (FI)
Vattulainen, I. (FI)
Martinez-Seara, Hector (UOCHB-X) RID, ORCIDArticle number e1005663 Source Title PLoS Computational Biology - ISSN 1553-734X
Roč. 13, č. 7 (2017)Number of pages 24 s. Language eng - English Country US - United States Keywords molecular simulations ; protein interaction ; N-glycosylation Subject RIV CF - Physical ; Theoretical Chemistry OECD category Physical chemistry R&D Projects GBP208/12/G016 GA ČR - Czech Science Foundation (CSF) Institutional support UOCHB-X - RVO:61388963 UT WOS 000406619800042 EID SCOPUS 85026671290 DOI 10.1371/journal.pcbi.1005663 Annotation 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. Workplace Institute of Organic Chemistry and Biochemistry Contact asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Viktorie Chládková, Tel.: 232 002 434 Year of Publishing 2018 Electronic address http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1005663
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