title: Circular permutation directs orthogonal assembly in complex collagen peptide mixtures.
abstract: Multiple types of natural collagens specifically assemble and co-exist in the extracellular matrix. Although noncollagenous trimerization domains facilitate the folding of triple-helical regions, it is intriguing to ask whether collagen sequences are also capable of controlling heterospecific association. In this study, we designed a model system mimicking simultaneous specific assembly of two collagen heterotrimers using a genetically inspired operation, circular permutation. Previously, surface charge-pair interactions were optimized on three collagen peptides to promote the formation of an abc-type heterotrimer. Circular permutation of these sequences retained networks of stabilizing interactions, preserving both triple-helical structure and heterospecificity of assembly. Combining original peptides A, B, and C and permuted peptides D, E, and F resulted primarily in formation of A:B:C and D:E:F, a heterospecificity of 2 of 56 possible stoichiometries. This degree of specificity in collagen molecular recognition is unprecedented in natural or synthetic collagens. Analysis of natural collagen sequences indicates low similarity between the neighboring exons. Combining the synthetic collagen model and bioinformatic analysis provides insight on how fibrillar collagens might have arisen from the duplication of smaller domains.
authors.affiliation: From the Center for Advanced Biotechnology and Medicine, Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, New Jersey 08854.
authors.forename: Fei
authors.initials: F
authors.lastname: Xu
authors.forename: Teresita
authors.initials: T
authors.lastname: Silva
authors.forename: Mihir
authors.initials: M
authors.lastname: Joshi
authors.forename: Sohail
authors.initials: S
authors.lastname: Zahid
authors.forename: Vikas
authors.initials: V
authors.lastname: Nanda
mesh_terms: D024022:Fibrillar Collagens / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D010455:Peptides / Q000235:genetics*; D017433:Protein Structure, Secondary
chemical_list: D024022:Fibrillar Collagens; D010455:Peptides
keywords: Circular Permutation; Collagen; Computer Modeling; Electrostatics; Fibrous Protein; Gene Duplication; Molecular Evolution; Molecular Recognition; Protein Design; Protein Self-assembly
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