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Direct observation of ligand-induced receptor dimerization with a bioresponsive hydrogel

Authors
Kim, JongseongPark, YongdooBrown, Ashley C.Lyon, L. Andrew
Issue Date
2014
Publisher
ROYAL SOC CHEMISTRY
Citation
RSC ADVANCES, v.4, no.110, pp.65173 - 65175
Indexed
SCIE
SCOPUS
Journal Title
RSC ADVANCES
Volume
4
Number
110
Start Page
65173
End Page
65175
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/101151
DOI
10.1039/c4ra13251c
ISSN
2046-2069
Abstract
Multimerization of biomolecules is essential for biological function and thus there is a need for sensitive biochemical assays that determine whether a molecule associates with one or more other molecules in the context of biological function. In this contribution we demonstrate a simple yet versatile method for the identification of physiologically important receptor dimerization events induced by a ligand. Bioresponsive hydrogel microparticles (microgels) conjugated with a receptor, Glycoprotein Ib alpha (GPIb alpha), display large changes in optical (microscopic) appearance under conditions known for to promote thrombin-induced GPIb alpha dimerization. In support of X-ray crystal structures, we identify that one thrombin molecule associates with two GPIb alpha moieties, which may play a role in efficient hemostatic function by increasing local concentration of GPIba on platelet surfaces. This microgel assay could provide a new way of studying important physiological and pathological mechanisms related to receptor dimerization and/or clustering.
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