Structural basis for the high-affinity interaction of nidogen-1 with immunoglobulin-like domain 3 of perlecan

Nidogen and perlecan are large multifunctional basement membrane (BM) prote ins conserved in all metazoa. Their high-affinity interaction, which is lik ely to contribute to BM assembly and function, is mediated by the central G 2 domain in nidogen and the third immunoglobulin (IG)-like domain in perIec an, IG3. We have solved the crystal structure at 2.0 Angstrom. resolution o f the mouse nidogen-1 G2-perlecan IG3 complex. Perlecan IG3 belongs to the I-set of the IG superfamily and binds to the wall of the nidogen-1 G2 beta -barrel using beta -strands C, D and F. Nidogen-1 residues participating in the extensive interface are highly conserved, whereas the corresponding bi nding site on perlecan is more variable. We hypothesize that a second, as y et unidentified, activity of nidogen overlaps with perlecan binding and acc ounts for the unusually high degree of surface conservation in the G2 domai n.