Gly-Gly-containing triplets of low stability adjacent to a type III collagen epitope.
Collagens, in addition to their structural role in the extracellular matrix, possess a number of functional binding domains. In this study, the binding to collagen of a monoclonal antibody is used as a model to define the molecular features involved in triple-helix interactions with other proteins. Here we report the thermal stability of an overlapping set of triple-helical peptides that includes the epitope recognized by a monoclonal antibody to type III collagen. Although the sequences of these peptides are very closely related, by a translation of a single triplet along the collagen chain, substantial variations in the melting temperatures were observed. These variations in thermal stability could not be readily explained by differences in imino acid content, or in numbers of charged or hydrophobic residues. The results indicate that Gly-Gly-Y triplets, which are adjacent to the epitope, have a strong influence in reducing the thermal stability of triple-helical peptides. Further studies, which were carried out on a set of "host-guest" triple-helical peptides containing different Gly-Gly-Y guest triplets, confirm the destabilizing effect of such tripeptides. The presence of Gly-Gly-Y triplets may play an important role in specific functions of type III collagen by modulating the local triple-helical structure or dynamics.
Shah
N K
NK
Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway 08854-5636, USA.
Sharma
M
M
Kirkpatrick
A
A
Ramshaw
J A
JA
Brodsky
B
B
D000595:Amino Acid Sequence; D003094:Collagen / Q000737:chemistry* / Q000276:immunology; D000939:Epitopes / Q000737:chemistry; D005998:Glycine / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013816:Thermodynamics
D000939:Epitopes; D010455:Peptides; D003094:Collagen; D005998:Glycine