Interruptions in the collagen repeating tripeptide pattern can promote supramolecular association. Protein Sci 2010 May;19(5):1053-64
Date
03/27/2010Pubmed ID
20340134Pubmed Central ID
PMC2868247DOI
10.1002/pro.383Scopus ID
2-s2.0-77951558891 (requires institutional sign-in at Scopus site) 25 CitationsAbstract
The standard collagen triple-helix requires a perfect (Gly-Xaa-Yaa)(n) sequence, yet all nonfibrillar collagens contain interruptions in this tripeptide repeating pattern. Defining the structural consequences of disruptions in the sequence pattern may shed light on the biological role of sequence interruptions, which have been suggested to play a role in molecular flexibility, collagen degradation, and ligand binding. Previous studies on model peptides with 1- and 4-residue interruptions showed a localized perturbation within the triple-helix, and this work is extended to introduce natural collagen interruptions up to nine residue in length within a fixed (Gly-Pro-Hyp)(n) peptide context. All peptides in this set show decreases in triple-helix content and stability, with greater conformational perturbations for the interruptions longer than five residue. The most stable and least perturbed structure is seen for the 5-residue interruption peptide, whose sequence corresponds to a Gly to Ala missense mutation, such as those leading to collagen genetic diseases. The triple-helix peptides containing 8- and 9-residue interruptions exhibit a strong propensity for self-association to fibrous structures. In addition, a small peptide modeling only the 9-residue sequence within the interruption aggregates to form amyloid-like fibrils with antiparallel beta-sheet structure. The 8- and 9-residue interruption sequences studied here are predicted to have significant cross-beta aggregation potential, and a similar propensity is reported for approximately 10% of other naturally occurring interruptions. The presence of amyloidogenic sequences within or between triple-helix domains may play a role in molecular association to normal tissue structures and could participate in observed interactions between collagen and amyloid.
Author List
Hwang ES, Thiagarajan G, Parmar AS, Brodsky BMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAmyloid
Calorimetry, Differential Scanning
Circular Dichroism
Collagen Type IV
Humans
Light
Microscopy, Electron
Molecular Sequence Data
Mutation, Missense
Oligopeptides
Protein Conformation
Protein Interaction Domains and Motifs
Protein Multimerization
Scattering, Radiation
