Localized unfolding of collagen explains collagenase cleavage near imino-poor sites.
Collagenases cleave all three chains of type III collagen at specific sites characterized by a Gly-Leu or a Gly-Ile bond that is upstream from an imino acid-poor region. Molecular dynamics trajectories were used to calculate the free energy of unfolding for collagen-like model peptides. The free energy profiles suggest that such imino-poor regions can adopt a low-energy, partially unfolded state where one of the peptide chains forms a solvent-exposed loop. The results are consistent with a model for collagenase cleavage where partial unfolding of imino-poor regions enables collagenases to gain access to their cleavage sites.
Stultz
Collin M
CM
Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA. cmstultz@partners.org
D000595:Amino Acid Sequence; D001665:Binding Sites; D024061:Collagen Type III / Q000737:chemistry* / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism*; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D016415:Sequence Alignment; D013816:Thermodynamics
D024061:Collagen Type III; D017364:Collagenases