Contribution of tertiary amides to the conformational stability of collagen triple helices

Abstract

The collagen triple helix is composed of three polypeptide strands, each with a sequence of repeating (Xaa-Yaa-Gly) triplets. In these triplets, Xaa and Yaa are often tertiary amides: L-proline (Pro) and 4(R)-hydroxy-L-proline (Hyp). To determine the contribution of tertiary amides to triple-helical stability, Pro and Hyp were replaced in synthetic collagen mimics with a non-natural acyclic tertiary amide: N-methyl-L-alanine (meAla). Replacing a Pro or Hyp residue with meAla decreases triple-helical stability. Ramachandran analysis indicates that meAla residues prefer to adopt straight phi and psi angles that are dissimilar from those of the Pro and Hyp residues in the collagen triple helix. Replacement with meAla decreases triple-helical stability more than does replacement with Ala. All of the peptide bonds in triple-helical collagen are in the trans conformation. Although an Ala residue greatly prefers the trans conformation, a meAla residue exists as a nearly equimolar mixture of trans and cis conformers. These findings indicate that the favorable contribution of Pro and Hyp to the conformational stability of collagen triple helices arises from factors other than their being tertiary amides.

Correlation analysis between single nucleotide polymorphisms of pulmonary surfactant protein A gene and pulmonary tuberculosis in the Han population in China

“…When proline is replaced by alanine, the triple helical structure of the SP-A protein is unstable, affecting the normal function of SP-A. 35 A synonymous mutation occurred at aa140 in SFTPA2. The SNP at aa140 may interfere with the shear and modification of mRNA because the locus aa140 is located near the splicing region of introns and exons, affecting the function of SP-A.…”

Synthesis and biological applications of collagen-model triple-helical peptides

“…156 A host-guest approach was used in which (Pro-Hyp-Gly) 7 was the control peptide, to examine the role of tertiary amides for the stability of triple-helical structure. 157 The middle Pro-Hyp-Gly triplet was substituted by N-methylalanine (meAla) in the Xxx or Yyy position, Ala in the Xxx or Yyy positions, or Pro in the Yyy position. Overall, meAla was found to be more destabilizing in either the Xxx or Yyy position than Ala, leading the authors to conclude that the presence of a tertiary amide is not sufficient for conformational stabilization of the triple-helix.…”

Tethering a laminin peptide to a crosslinked collagen scaffold for biofunctionality

“…37 The triple helical conformation of collagen was attributed to the hydrogen bond which links the carbonyl or hydroxyl groups in the three chains of the peptide. 38 Thus the conformational changes in the spectrum in the laminin peptide tethered to mTGase crosslinked scaffold indicates that the structural changes in the collagen assembly due to the crosslinking activity of mTGase is due to the presence of laminin peptide. The conformational preference of collagen with various concentrations of laminin peptide was studied by CD spectroscopy.…”