Homology models for domains 21-23 of human tropoelastin shed light on lysine crosslinking.
The contiguous crosslinking domain at the center of human tropoelastin encoded by exons 21-23 contains an unusual 'hinge' region thought to adopt both open and closed conformations. Key lysines 425 and 437 have been implicated in both artificial and lysyl oxidase mediated crosslinks. We have examined the importance of hinge conformation to the proximity of these lysines and their ability to undergo intramolecular and intermolecular crosslinks using homology models. The results, counter intuitively, indicate that the more open hinge conformations favor intramolecular crosslinking, while the more closed conformations favor intermolecular crosslinking. We also present evidence that the sidechains of lysines 425 and 437 are able to make direct contact enabling an intramolecular lysyl oxidase mediated crosslink.
Dyksterhuis
L B
LB
Molecular and Health Technologies, CSIRO, Victoria 3168, Australia. leanne@dyksterhuis.com
Weiss
A S
AS
D006801:Humans; D008239:Lysine / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D017434:Protein Structure, Tertiary / Q000235:genetics; D008249:Protein-Lysine 6-Oxidase / Q000737:chemistry; D040681:Structural Homology, Protein; D014333:Tropoelastin / Q000737:chemistry* / Q000235:genetics
D014333:Tropoelastin; D008249:Protein-Lysine 6-Oxidase; D008239:Lysine