Gly-X-Y tripeptide frequencies in collagen: a context for host-guest triple-helical peptides.

The collagen triple-helix consists of a repeating (Gly-X-Y)n sequence. In theory, there are more than 400 possible Gly-X-Y triplets, but analysis of sequences from fibrillar and nonfibrillar collagens shows that only a limited set of triplets are found in significant numbers, and many are never observed. The nonrandom frequency of Gly-X-Y triplets makes it practical to experimentally approach the stability of much of the collagen sequence through the study of a limited set of host-guest peptides. In these peptides, individual Gly-X-Y triplets constitute the guest, while the host consists of Gly-Pro-Hyp tripeptides. A set of host-guest peptides was designed to contain the most common nonpolar and charged triplets found in collagen. All formed stable triple-helices, with their melting temperature depending on the identity of the guest triplet. While including less than 10% of all possible triplets, the data set covers 50-60% of collagen sequences and provides a starting point for establishing a stability scale to predict the relative stability of important collagen regions, such as the matrix metalloproteinase cleavage site or binding sites.

[1]  J. Ramshaw,et al.  A host-guest set of triple-helical peptides: stability of Gly-X-Y triplets containing common nonpolar residues. , 1996, Biochemistry.

[2]  Beat Steinmann,et al.  Connective tissue and its heritable disorders —Molecular, genetic and medical aspects , 1993 .

[3]  J. Ramshaw,et al.  Gly-Gly-containing triplets of low stability adjacent to a type III collagen epitope. , 1997, Biochemistry.

[4]  H. Bächinger,et al.  Sequence specific thermal stability of the collagen triple helix. , 1991, International journal of biological macromolecules.

[5]  G. Fields,et al.  A model for interstitial collagen catabolism by mammalian collagenases. , 1991, Journal of theoretical biology.

[6]  K. Kadler.  Extracellular matrix 1: Fibril-forming collagens. , 1995, Protein profile.

[7]  W. Traub,et al.  Conformational implications of amino acid sequence regularities in collagen , 1975, FEBS letters.

[8]  L Regan,et al.  A thermodynamic scale for the beta-sheet forming tendencies of the amino acids. , 1994, Biochemistry.

[9]  A. Fersht,et al.  Alpha-helix stability in proteins. II. Factors that influence stability at an internal position. , 1992, Journal of molecular biology.

[10]  J. Ramshaw,et al.  Gly-Pro-Arg Confers Stability Similar to Gly-Pro-Hyp in the Collagen Triple-helix of Host-Guest Peptides* , 1997, The Journal of Biological Chemistry.

[11]  J. Werkmeister,et al.  Identification of the epitope for a monoclonal antibody that blocks platelet aggregation induced by type III collagen. , 1997, Biochemical Journal.

[12]  W. Roth,et al.  Synthesis and investigation of collagen model peptides , 1982 .

[13]  G. N. Ramachandran,et al.  A theoretical study of the structures of (Gly-Pro-Leu)n and (Gly-Leu-Pro)n. , 2009, International journal of peptide and protein research.

[14]  J. Ramshaw,et al.  Positional Preferences of Ionizable Residues in Gly-X-YTriplets of the Collagen Triple-helix* , 1997, The Journal of Biological Chemistry.

[15]  W. DeGrado,et al.  A thermodynamic scale for the helix-forming tendencies of the commonly occurring amino acids. , 1990, Science.

[16]  F. Crick,et al.  The molecular structure of collagen. , 1961, Journal of molecular biology.

[17]  H M Berman,et al.  Crystal and molecular structure of a collagen-like peptide at 1.9 A resolution. , 1994, Science.

[18]  C. Levene.  Book Review: Treatise on Collagen , 1969 .

[19]  N. Morris,et al.  Thermal stability and folding of the collagen triple helix and the effects of mutations in osteogenesis imperfecta on the triple helix of type I collagen. , 1993, American journal of medical genetics.

[20]  J. Baum,et al.  Characterization of collagen-like peptides containing interruptions in the repeating Gly-X-Y sequence. , 1993, Biochemistry.

[21]  D J Prockop,et al.  Collagens: molecular biology, diseases, and potentials for therapy. , 1995, Annual review of biochemistry.

[22]  J. Baum,et al.  Backbone dynamics of (Pro-Hyp-Gly)10 and a designed collagen-like triple-helical peptide by 15N NMR relaxation and hydrogen-exchange measurements. , 1993, Biochemistry.

[23]  E. Jones,et al.  Analysis of structural design features in collagen. , 1991, Journal of molecular biology.

[24]  J. Ramshaw,et al.  Electrostatic interactions in collagen-like triple-helical peptides. , 1994, Biochemistry.

[25]  P. S. Kim,et al.  Measurement of the β-sheet-forming propensities of amino acids , 1994, Nature.

[26]  R A Berg,et al.  The thermal transition of a non-hydroxylated form of collagen. Evidence for a role for hydroxyproline in stabilizing the triple-helix of collagen. , 1973, Biochemical and biophysical research communications.

[27]  K. Beck,et al.  Supercoiled Protein Motifs: The Collagen Triple-Helix and the α-Helical Coiled Coil , 1998 .

[28]  E. Heidemann,et al.  Influence of different tripeptides on the stability of the collagen triple helix. I. Analysis of the collagen sequence and identification of typical tripeptides , 1986, Biopolymers.

[29]  R. L. Baldwin,et al.  Helix propensities of the amino acids measured in alanine‐based peptides without helix‐stabilizing side‐chain interactions , 1994, Protein science : a publication of the Protein Society.

[30]  E. Stellwagen,et al.  Residue helix parameters obtained from dichroic analysis of peptides of defined sequence. , 1993, Biochemistry.

[31]  R. Fraser,et al.  Chain conformation in the collagen molecule. , 1979, Journal of molecular biology.