Oligomerisation and thermal stability of polyvalent integrin [alpha]5[beta]1 ligands

Kreiner, M., Byron, O., Domingues, D. and van der Walle, C.F. (2009) Oligomerisation and thermal stability of polyvalent integrin [alpha]5[beta]1 ligands. Biophysical Chemistry, 142(1-3), pp. 34-39. (doi: 10.1016/j.bpc.2009.03.001)

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Publisher's URL: http://dx.doi.org/10.1016/j.bpc.2009.03.001

Abstract

Synthetic oligomeric integrin [alpha]5[beta]1 ligands, specifically immobilised to surfaces, facilitate increased fibroblast cell spreading compared with that associated with the monomer. These ligands consist of a N-terminal fibronectin domain pair, a spacer and a di-, tri- or tetrameric coiled coil. However, it is not yet clear what effect fusion of the fibronectin domains has on the predicted oligomerisation of the coiled coils. Using analytical ultracentrifugation we show that the predicted tetrameric and trimeric coiled coils facilitate a corresponding ligand oligomerisation with half-dissociation at 0.7 and 0.2 ÝM, respectively. In contrast, the predicted dimeric coiled coil formed both dimers and trimers. Under non-reducing conditions, the unique C-terminal thiol-facilitated inter-oligomer dimerisation of the trimeric species, generating hexameric ligands. Disulphide bonding also increased helical stability during thermal unfolding. The work allows the cellular response to these clustered integrin [alpha]5[beta]1 ligands to be more accurately interpreted, and has wider implications with respect to the utility of coiled coils as tools to facilitate protein oligomerisation

Item Type:Articles
Keywords:Coiled coil, fibronectin, integrin, analytical ultracentrifugation, thermal unfolding
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Byron, Professor Olwyn
Authors: Kreiner, M., Byron, O., Domingues, D., and van der Walle, C.F.
Subjects:Q Science > QH Natural history > QH345 Biochemistry
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Biophysical Chemistry
ISSN:0301-4622

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