title: NMR studies demonstrate a unique AAB composition and chain register for a heterotrimeric type IV collagen model peptide containing a natural interruption site.
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.
authors.affiliation: the Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China, From the Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey 08854.
authors.forename: Jianxi
authors.initials: J
authors.lastname: Xiao
authors.affiliation: the Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China.
authors.forename: Xiuxia
authors.initials: X
authors.lastname: Sun
authors.affiliation: the Central Leather Research Institute, Council of Scientific and Industrial Research, Adyar, Chennai-600020, India.
authors.forename: Balaraman
authors.initials: B
authors.lastname: Madhan
authors.affiliation: the Department of Biomedical Engineering, Tufts University, Medford, Massachusetts 02446, and barbara.brodsky@tufts.edu.
authors.forename: Barbara
authors.initials: B
authors.lastname: Brodsky
authors.affiliation: From the Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey 08854, jean.baum@rutgers.edu.
authors.forename: Jean
authors.initials: J
authors.lastname: Baum
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002942:Circular Dichroism; D024141:Collagen Type IV / Q000737:chemistry*; D005109:Extracellular Matrix / Q000378:metabolism; D005998:Glycine / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D024041:Non-Fibrillar Collagens / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
chemical_list: D024141:Collagen Type IV; D024041:Non-Fibrillar Collagens; D010455:Peptides; D005998:Glycine
keywords: circular dichroism (CD); collagen; extracellular matrix; heterotrimer; interruption; nuclear magnetic resonance (NMR); structure-function