title: Sequence dependence of kinetics and morphology of collagen model peptide self-assembly into higher order structures.
abstract: The process of self-assembly of the triple-helical peptide (Pro-Hyp-Gly)(10) into higher order structure resembles the nucleation-growth mechanism of collagen fibril formation in many features, but the irregular morphology of the self-assembled peptide contrasts with the ordered fibers and networks formed by collagen in vivo. The amino acid sequence in the central region of the (Pro-Hyp-Gly)(10) peptide was varied and found to affect the kinetics of self-assembly and nature of the higher order structure formed. Single amino acid changes in the central triplet produced irregular higher order structures similar to (Pro-Hyp-Gly)(10), but the rate of self-association was markedly delayed by a single change in one Pro to Ala or Leu. The introduction of a Hyp-rich hydrophobic sequence from type IV collagen resulted in a more regular suprastructure of extended fibers that sometimes showed supercoiling and branching features similar to those seen for type IV collagen in the basement membrane network. Several peptides, where central Pro-Hyp sequences were replaced by charged residues or a nine-residue hydrophobic region from type III collagen, lost the ability to self-associate under standard conditions. The inability to self-assemble likely results from loss of imino acids, and lack of an appropriate distribution of hydrophobic/electrostatic residues. The effect of replacement of a single Gly residue was also examined, as a model for collagen diseases such as osteogenesis imperfecta and Alport syndrome. Unexpectedly, the Gly to Ala replacement interfered with self-assembly of (Pro-Hyp-Gly)(10), while the peptide with a Gly to Ser substitution self-associated to form a fibrillar structure.
authors.affiliation: Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854, USA.
authors.forename: Karunakar
authors.initials: K
authors.lastname: Kar
authors.forename: Yuh-Hwa
authors.initials: YH
authors.lastname: Wang
authors.forename: Barbara
authors.initials: B
authors.lastname: Brodsky
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D003094:Collagen / Q000737:chemistry*; D007700:Kinetics; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry*; D011487:Protein Conformation; D055672:Static Electricity
chemical_list: D009842:Oligopeptides; D003094:Collagen