SOLUTION STRUCTURE OF THE LINK MODULE - A HYALURONAN-BINDING DOMAIN INVOLVED IN EXTRACELLULAR-MATRIX STABILITY AND CELL-MIGRATION

Link modules are hyaluronan-binding domains found in proteins involved in the assembly of extracellular matrix, cell adhesion, and migration . The solution structure of the Link module from human TSG-6 was deter mined and found to consist of two alpha helices and two antiparallel b eta sheets arranged around a large hydrophobic core. This defines the consensus fold for the Link module superfamily, which includes CD44, c artilage link protein, and aggrecan. The TSG-6 Link module was shown t o interact with hyaluronan, and a putative binding surface was identif ied on the structure. A structural database search revealed close simi larity between the Link module and the C-type lectin domain, with the predicted hyaluronan-binding site at an analogous position to the carb ohydrate-binding pocket in E-selectin.