title: Peptide investigations of pairwise interactions in the collagen triple-helix.
abstract: Pairwise interactions have been studied for the major secondary structures in proteins. The present work extends the characterization of interactions between side-chains to the context of a collagen triple-helix. In this study, the most frequent Gly-X-Y tripeptide sequences in collagen are characterized in terms of interchain interactions between non-imino acid X and Y residues, through the use of host-guest peptides and statistical frequency analysis. Stabilities predicted on the basis of additivity show good agreement with experimental values for almost half of the peptides, indicating a lack of interaction. A small number of peptides have a stability lower than predicted, while a larger number are more stable than expected. Of all triplets containing residues of opposite charge, only Gly-Lys-Asp and Gly-Arg-Asp exhibit stabilizing electrostatic interactions, and these pairs are found together preferentially in collagens. Repulsion of like charges is observed in Gly-Arg-Lys, Gly-Lys-Arg, and Gly-Glu-Asp sequences, and a small degree of hydrophobic stabilization was observed for the Gly-Leu-Leu guest triplet. The data reported here help clarify basic principles of triple-helix stability. In addition, the experimentally determined stabilities of the tripeptide units found most frequently in collagens constitute a database useful for predicting triple-helix stability in peptides, collagens and other triple-helix-containing proteins.
authors.affiliation: Department of Biochemistry, UMDNJ - Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA.
authors.forename: Anton V
authors.initials: AV
authors.lastname: Persikov
authors.forename: John A M
authors.initials: JA
authors.lastname: Ramshaw
authors.forename: Alan
authors.initials: A
authors.lastname: Kirkpatrick
authors.forename: Barbara
authors.initials: B
authors.lastname: Brodsky
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D003094:Collagen / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D013329:Structure-Activity Relationship; D013696:Temperature; D013816:Thermodynamics
chemical_list: D010455:Peptides; D003094:Collagen