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.
Highlights
Heterotrimeric type IV collagen has breaks in the triple-helix repeating Gly-X-Y sequence
We have previously reported a study on a heterotrimer composed of two peptides designed to model a natural interruption site in the triple helical domain of the most abundant isoform, [␣1(IV)]2␣2(IV) of type IV collagen [30]
For the heterotrimeric type IV collagen, ϳ20 of these sequence discontinuities are distributed throughout the triple-helix, and they may play significant roles in the organization and mechanical integrity of basement membranes
Summary
Heterotrimeric type IV collagen has breaks in the triple-helix repeating Gly-X-Y sequence. 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. There are more than 350 interruptions found in non-fibrillar collagen chains, such as the ϳ20 breaks in the Gly-X-Y repeating pattern seen in the triple-helix domain of type IV collagen chains in basement membranes. These natural interruptions in the collagen triple-helix are suggested to play important roles in molecular structure, selfassociation, binding, and degradation (9 –14). When the two peptides were mixed in a 2:1 ratio, a singlecomponent heterotrimer was observed with a defined register ␣1␣1␣2(IV) and with interchain hydrogen bonds at the interruption site
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