Crystal structures of the network-forming short-arm tips of the laminin ?1 and ?1 chains.

ABSTRACT: The heterotrimeric laminins are a defining component of basement membranes and essential for tissue formation and function in all animals. The three short arms of the cross-shaped laminin molecule are composed of one chain each and their tips mediate the formation of a polymeric network. The structural basis for laminin polymerisation is unknown. We have determined crystal structures of the short-arm tips of the mouse laminin ?1 and ?1 chains, which are grossly similar to the previously determined structure of the corresponding ?5 chain region. The short-arm tips consist of a laminin N-terminal (LN) domain that is attached like the head of a flower to a rod-like stem formed by tandem laminin-type epidermal growth factor-like (LE) domains. The LN domain is a ?-sandwich with elaborate loop regions that differ between chains. The ?1 LN domain uniquely contains a calcium binding site. The LE domains have little regular structure and are stabilised by cysteines that are disulphide-linked 1-3, 2-4, 5-6 and 7-8 in all chains. The LN surface is not conserved across the ?, ? and ? chains, but within each chain subfamily there is a striking concentration of conserved residues on one face of the ?-sandwich, while the opposite face invariably is shielded by glycans. We propose that the extensive conserved patches on the ? and ? LN domains mediate the binding of these two chains to each other, and that the ? chain LN domain subsequently binds to the composite ?-? surface. Mutations in the laminin ?2 LN domain causing Pierson syndrome are likely to impair the folding of the ?2 chain or its ability to form network interactions.

SUBMITTER: Carafoli F 

PROVIDER: S-EPMC3409155 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature