Disulfide bond formation through Cys186 facilitates functionally relevant dimerization of trimeric hyaluronanâbinding protein 1 (HABP1)/p32/gC1qR
2002
Jha, Babal Kant | Salunke, Dinakar M. | Datta, Kasturi
Hyaluronanâbinding proteinâ1 (HABP1), a ubiquitous multifunctional protein, interacts with hyaluronan, globular head of complement component 1q (gC1q), and clustered mannose and has been shown to be involved in cell signalling. Inâvitro, this recombinant protein isolated from human fibroblast exists in different oligomeric forms, as is evident from the results of various independent techniques in nearâphysiological conditions. As shown by sizeâexclusion chromatography under various conditions and glutaraldehyde crossâlinking, HABP1 exists as a noncovalently associated trimer in equilibrium with a small fraction of a covalently linked dimer of trimers, i.e. a hexamer. The formation of a covalentlyâlinked hexamer of HABP1 through Cys186 as a dimer of trimers is achieved by thiol group oxidation, which can be blocked by modification of Cys186. The gradual structural transition caused by cysteineâmediated disulfide linkage is evident as the fluorescence intensity increases with increasing Hg2+ concentration until all the HABP1 trimer is converted into hexamer. In order to understand the functional implication of these transitions, we examined the affinity of the hexamer for different ligands. The hexamer shows enhanced affinity for hyaluronan, gC1q, and mannosylated BSA compared with the trimeric form. Our data, analyzed with reference to the HABP1/p32 crystal structure, suggest that the oligomerization state and the compactness of its structure are factors that regulate its function.
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