Insertion of Pro-Hyp-Gly provides 2 kcal mol?1stability but attenuates the specific assembly of ABC heterotrimeric collagen triple helices
Journal
Organic and Biomolecular Chemistry
Journal Volume
19
Journal Issue
8
Pages
1860-1866
Date Issued
2021
Author(s)
Abstract
Collagen is a major structural component of the extracellular matrix and connective tissue. The key structural feature of collagen is the collagen triple helix, with a Xaa-Yaa-Gly (glycine) repeating pattern. The most frequently occurring triplet is Pro (proline)-Hyp (hydroxyproline)-Gly. The reversible thermal folding and unfolding of a series of heterotrimeric collagen triple helices with varying number of Pro-Hyp-Gly triplets were monitored by circular dichroism spectroscopy to determine the unfolding thermodynamic parametersTm(midpoint transition temperature), ΔHTm(unfolding enthalpy), and ΔGunfold(unfolding free energy). TheTmand ΔGunfoldof the heterotrimeric collagen triple helices increased with increasing number of Pro-Hyp-Gly triplets. The ΔGunfoldincreased by 2.0 ± 0.2 kcal mol?1upon inserting one Pro-Hyp-Gly triplet into all three chains. TheTmdifference between the most stable ABC combination and the second most stable BCC combination decreased with increasing number of Pro-Hyp-Gly triplets, even though the ΔGunfolddifference remained the same. These results should be useful for tuning the stability of collagen triple helical peptides for hydrogel formation, recognition of denatured collagen triple helices as diagnostics and therapeutics, and targeted drug delivery. ? The Royal Society of Chemistry 2021.
Subjects
Circular dichroism spectroscopy; Dichroism; Free energy; Hydroxyproline; Musculoskeletal system; Targeted drug delivery; Collagen triple helix; Denatured collagen; Extracellular matrices; Folding and unfolding; Hydrogel formation; Repeating patterns; Structural component; Structural feature; Collagen
Type
journal article