The role in cell binding of a beta-bend within the triple helical region in collagen alpha 1 (I) chain: structural and biological evidence for conformational tautomerism on fiber surface

J Biomol Struct Dyn. 1997 Apr;14(5):547-60. doi: 10.1080/07391102.1997.10508155.


In its physiological solid state, type I collagen serves as a host for many types of cells. Only the molecules on fiber surface are available for interaction. In this interfacial environment, the conformation of a cell binding domain can be expected to fluctuate between the collagen fold and a distinctive non-collagen molecular marker for recognition and allosteric binding. If the cell binding domain can be localized in contiguous residues within the exposed half of a turn of the triple helix (approximately 15 residues), the need for extensive structural modification and unraveling of the triple helix is avoided. We examined the conformational preferences and biological activity of a synthetic 15-residue peptide (P-15), analogous to the sequence 766GTPGPQGIAGQRGVV780 in the alpha 1 (I) chain. Theoretical studies showed a high potential for a stable beta-bend for the central GIAG sequence. The flanking sequences showed facile transition to extended conformations. Circular dichroism of the synthetic peptide in anisotropic solvents confirmed the presence of beta-strand and beta-bend structures. P-15 inhibited fibroblast binding to collagen in a concentration dependent manner, with near maximal inhibition occurring at a concentration of 7.2 x 10(-6) M. The temporal pattern of cell attachment was altered markedly in the presence of P-15. No inhibition was seen with a peptide P-15(AI), an analogue of P-15 with the central IA residues reversed to AI or with collagen-related peptides (Pro-Pro-Gly)10, (Pro-Hyp-Gly)10, and polyproline, and with several unrelated peptides. Our studies suggest a molecular mechanism for cell binding to collagen fibers based on a conformational transition in collagen molecules on the fiber surface. Since the energy barrier between the collagen fold and beta-strand conformation is low, a local conformational change may be possible in molecules on the fiber surface because of their location in an anisotropic environment. Our observations also suggest that the sequence incorporated in P-15 may be a specific ligand for cells. Unlike other reported cell binding peptides, the residues involved in this interaction are non-polar.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Allosteric Regulation
  • Allosteric Site
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cell Division
  • Cells, Cultured
  • Collagen / chemistry*
  • Collagen / metabolism*
  • Computer Graphics
  • Fibroblasts
  • Humans
  • Infant, Newborn
  • Isomerism
  • Macromolecular Substances
  • Metalloendopeptidases / biosynthesis
  • Models, Molecular
  • Molecular Sequence Data
  • Peptide Fragments / chemistry*
  • Protein Structure, Secondary*
  • Rats
  • Skin / cytology*
  • Skin Physiological Phenomena
  • Software
  • Surface Properties


  • Macromolecular Substances
  • Peptide Fragments
  • Collagen
  • Metalloendopeptidases