Supramolecular organization of the ?121-?565 collagen IV network.

ABSTRACT: Collagen IV is a family of 6 chains (?1-?6), that form triple-helical protomers that assemble into supramolecular networks. Two distinct networks with chain compositions of ?121 and ?345 have been established. These oligomerize into separate ?121 and ?345 networks by a homotypic interaction through their trimeric noncollagenous (NC1) domains, forming ?121 and ?345 NC1 hexamers, respectively. These are stabilized by novel sulfilimine (-S=N-) cross-links, a covalent cross-link that forms between Met(93) and Hyl(211) at the trimer-trimer interface. A third network with a composition of ?1256 has been proposed, but its supramolecular organization has not been established. In this study we investigated the supramolecular organization of this network by determining the chain identity of sulfilimine-cross-linked NC1 domains derived from the ?1256 NC1 hexamer. High resolution mass spectrometry analyses of peptides revealed that sulfilimine bonds specifically cross-link ?1 to ?5 and ?2 to ?6 NC1 domains, thus providing the spatial orientation between interacting ?121 and ?565 trimers. Using this information, we constructed a three-dimensional homology model in which the ?565 trimer shows a good chemical and structural complementarity to the ?121 trimer. Our studies provide the first chemical evidence for an ?565 protomer and its heterotypic interaction with the ?121 protomer. Moreover, our findings, in conjunction with our previous studies, establish that the six collagen IV chains are organized into three canonical protomers ?121, ?345, and ?565 forming three distinct networks: ?121, ?345, and ?121-?565, each of which is stabilized by sulfilimine bonds between their C-terminal NC1 domains.

SUBMITTER: Robertson WE 

PROVIDER: S-EPMC4162165 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature