title: Aromatic interactions promote self-association of collagen triple-helical peptides to higher-order structures.
abstract: Aromatic residues are relatively rare within the collagen triple helix, but they appear to play a specialized role in higher-order structure and function. The role of aromatic amino acids in the self-assembly of triple-helical peptides was investigated in terms of the kinetics of self-association, the nature of aggregated species formed, and the ability of these species to activate platelet aggregation. The presence of aromatic residues on both ends of a type IV collagen model peptide is observed to greatly accelerate the kinetics of self-association, decreasing the lag time and leading to insoluble, well-defined linear fibrils as well as small soluble aggregates. Both macroscopic visible aggregates and small multimolecular complexes in solution are capable of inducing platelet aggregation through the glycoprotein VI receptor on platelets. Proline-aromatic CH...pi interactions are often observed within globular proteins and in protein complexes, and examination of molecular packing in the crystal structure of the integrin binding collagen peptide shows Phe interacts with Pro/Hyp in a neighboring triple-helical molecule. An intermolecular interaction between aromatic amino acids and imino acids within the triple helix is also supported by the observed inhibitory effect of isolated Phe amino acids on the self-association of (Pro-Hyp-Gly)(10). Given the high fraction of Pro and Hyp residues on the surface of collagen molecules, it is likely that imino acid-aromatic CH...pi interactions are important in formation of higher-order structure. We suggest that the catalysis of type I collagen fibrillogenesis by nonhelical telopeptides is due to specific intermolecular CH...pi interactions between aromatic residues in the telopeptides and Pro/Hyp residues within the triple helix.
authors.affiliation: Department of Biochemistry, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
authors.forename: Karunakar
authors.initials: K
authors.lastname: Kar
authors.forename: Sajjad
authors.initials: S
authors.lastname: Ibrar
authors.forename: Vikas
authors.initials: V
authors.lastname: Nanda
authors.forename: Todd M
authors.initials: TM
authors.lastname: Getz
authors.forename: Satya P
authors.initials: SP
authors.lastname: Kunapuli
authors.forename: Barbara
authors.initials: B
authors.lastname: Brodsky
mesh_terms: D000595:Amino Acid Sequence; D024322:Amino Acids, Aromatic / Q000737:chemistry* / Q000378:metabolism; D024141:Collagen Type IV / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D003460:Crystallization; D018360:Crystallography, X-Ray; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D010649:Phenylalanine / Q000737:chemistry / Q000378:metabolism; D015539:Platelet Activation; D017433:Protein Structure, Secondary; D012995:Solubility
chemical_list: D024322:Amino Acids, Aromatic; D024141:Collagen Type IV; D010455:Peptides; D010649:Phenylalanine