The NC2 Domain of Collagen IX Provides Chain Selection and Heterotrimerization |
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| Authors: | Sergei P. Boudko Keith D. Zientek Jesse Vance Jessica L. Hacker Jürgen Engel Hans Peter B?chinger |
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| Affiliation: | From the ‡Research Department, Shriners Hospital for Children, Portland, Oregon 97239.;the §Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, Oregon 97239, and ;the ¶Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland |
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| Abstract: | The mechanism of chain selection and trimerization of fibril-associated collagens with interrupted triple helices (FACITs) differs from that of fibrillar collagens that have special C-propeptides. We recently showed that the second carboxyl-terminal non-collagenous domain (NC2) of homotrimeric collagen XIX forms a stable trimer and substantially stabilizes a collagen triple helix attached to either end. We then hypothesized a general trimerizing role for the NC2 domain in other FACITs. Here we analyzed the NC2 domain of human heterotrimeric collagen IX, the only member of FACITs with all three chains encoded by distinct genes. Upon oxidative folding of equimolar amounts of the α1, α2, and α3 chains of NC2, a stable heterotrimer with a disulfide bridge between α1 and α3 chains is formed. Our experiments show that this heterotrimerization domain can stabilize a short triple helix attached at the carboxyl-terminal end and allows for the proper oxidation of the cystine knot of type III collagen after the short triple helix. |
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| Keywords: | Collagen Extracellular Matrix Proteins Protein Domains Protein Folding Protein Self-assembly Collagen IX FACITs NC2 Domain Heterotrimerization Domain |
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