Atomistic fingerprint of hyaluronan-CD44 binding
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F17%3A00478304" target="_blank" >RIV/61388963:_____/17:00478304 - isvavai.cz</a>
Result on the web
<a href="http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1005663" target="_blank" >http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1005663</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1371/journal.pcbi.1005663" target="_blank" >10.1371/journal.pcbi.1005663</a>
Alternative languages
Result language
angličtina
Original language name
Atomistic fingerprint of hyaluronan-CD44 binding
Original language description
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.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10403 - Physical chemistry
Result continuities
Project
<a href="/en/project/GBP208%2F12%2FG016" target="_blank" >GBP208/12/G016: Controlling structure and function of biomolecules at the molecular scale: theory meets experiment</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
PLoS Computational Biology
ISSN
1553-734X
e-ISSN
—
Volume of the periodical
13
Issue of the periodical within the volume
7
Country of publishing house
US - UNITED STATES
Number of pages
24
Pages from-to
—
UT code for WoS article
000406619800042
EID of the result in the Scopus database
2-s2.0-85026671290