Abstract
All non-fibrillar collagens contain interruptions in the (Gly-X-Y)n repeating sequence, such as the more than 20 interruptions found in chains of basement membrane type IV collagen. Two selectively doubly labeled peptides are designed to model a site in type IV collagen with a GVG interruption in the α1(IV) and a corresponding GISLK sequence within the α2(IV) chain. CD and NMR studies on a 2:1 mixture of these two peptides support the formation of a single-component heterotrimer that maintains the one-residue staggering in the triple-helix, has a unique chain register, and contains hydrogen bonds at the interruption site. Formation of hydrogen bonds at interruption sites may provide a driving force for self-assembly and chain register in type IV and other non-fibrillar collagens. This study illustrates the potential role of interruptions in the structure, dynamics, and folding of natural collagen heterotrimers and forms a basis for understanding their biological role.
Background: Heterotrimeric type IV collagen has breaks in the triple-helix repeating Gly-X-Y sequence.
Results: NMR studies on a type IV peptide model show heterotrimeric chain selection and register, with new hydrogen bonds formed at an interruption site.
Conclusion: Interruption sites may provide a driving force for self-assembly and chain register.
Significance: Interruptions can have a positive effect on triple-helix continuity in non-fibrillar heterotrimer collagens.