Contribution of tertiary amides to the conformational stability of collagen triple helices.
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.
Kersteen
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EA
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706.
Raines
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RT
D019943:Amino Acid Substitution; D000818:Animals; D003094:Collagen / Q000737:chemistry* / Q000648:ultrastructure; D006801:Humans; D006909:Hydroxyproline / Q000494:pharmacology*; D011392:Proline / Q000494:pharmacology*; D011489:Protein Denaturation; D017434:Protein Structure, Tertiary / Q000187:drug effects
D003094:Collagen; D011392:Proline; D006909:Hydroxyproline