title: Is glycine a surrogate for a D-amino acid in the collagen triple helix?
abstract: Collagen is the most abundant protein in animals. Every third residue in a collagen strand is a glycine with phi, psi = -70 degrees, 175 degrees. A recent computational study suggested that replacing these glycine residues with D-alanine or D-serine would stabilize the collagen triple helix. This hypothesis is of substantial importance, as the glycine residues in collagen constitute nearly 10% of the amino acid residues in humans. To test this hypothesis, we synthesized a series of collagen mimic peptides that contain one or more D-alanine or D-serine residues replacing the canonical glycine residues. Circular dichroism spectroscopy and thermal denaturation experiments indicated clearly that the substitution of glycine with D-alanine or D-serine greatly disfavors the formation of a triple helix. Host-guest studies also revealed that replacing a single glycine residue with D-alanine is more destabilizing than is its replacement with L-alanine, a substitution that results from a common mutation in patients with collagen-related diseases. These data indicate that the glycine residues in collagen are not a surrogate for a D-amino acid and support the notion that the main-chain torsion angles of a glycine residue in the native structure (especially, phi > 0 degrees ) are critical determinants for its beneficial substitution with a D-amino acid in a protein.
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706, USA.
authors.forename: Jia-Cherng
authors.initials: JC
authors.lastname: Horng
authors.forename: Frank W
authors.initials: FW
authors.lastname: Kotch
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Raines
mesh_terms: D000409:Alanine / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry*; D002942:Circular Dichroism; D003094:Collagen / Q000737:chemistry*; D005998:Glycine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D012694:Serine / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D010455:Peptides; D012694:Serine; D003094:Collagen; D000409:Alanine; D005998:Glycine