Is glycine a surrogate for a D-amino acid in the collagen triple helix?
| Autor: | Frank W. Kotch, Jia-Cherng Horng, Ronald T. Raines |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Protein Folding
Circular dichroism Magnetic Resonance Spectroscopy Protein Conformation Stereochemistry Collagen helix Glycine Biochemistry Article Serine Protein structure Amino Acids Molecular Biology chemistry.chemical_classification Alanine Molecular Structure Chemistry Circular Dichroism Amino acid Models Chemical Thermodynamics Protein folding Collagen Peptides Triple helix |
| Zdroj: | Protein Science. 16:208-215 |
| ISSN: | 1469-896X 0961-8368 |
| Popis: | 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, phi0 degrees ) are critical determinants for its beneficial substitution with a D-amino acid in a protein. |
| Databáze: | OpenAIRE |
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