title: The structure of a 19-residue fragment from the C-loop of the fourth epidermal growth factor-like domain of thrombomodulin.
abstract: The solution structure has been determined for a 19-residue peptide that is fully folded at room temperature. The sequence of this peptide is based on the C-loop, residues 371-389, of the fourth epidermal growth factor-like domain of thrombomodulin, a protein that acts as a cofactor for the thrombin activation of protein C. Despite its small size, the peptide forms a compact structure with almost no repeating secondary structure. The results indicate the structure is held together by hydrophobic interactions, which in turn stabilize the two beta-turns in the structure. The first beta-turn in the C-loop represents a conserved motif that is found in the published structures of five other epidermal growth factor-like proteins. The critical role of Phe376 in the stabilization of the first beta-turn is consistent with mutagenesis data with soluble thrombomodulin. The results also show that a small subdomain of a larger protein can fold independently, and therefore it could act as an initiation site for further folding.
authors.affiliation: Berlex Bioscience, Inc., Richmond, California 94804-0099, USA.
authors.forename: M
authors.initials: M
authors.lastname: Adler
authors.forename: M H
authors.initials: MH
authors.lastname: Seto
authors.forename: D E
authors.initials: DE
authors.lastname: Nitecki
authors.forename: J H
authors.initials: JH
authors.lastname: Lin
authors.forename: D R
authors.initials: DR
authors.lastname: Light
authors.forename: J
authors.initials: J
authors.lastname: Morser
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004355:Drug Stability; D004815:Epidermal Growth Factor / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D018180:Thrombomodulin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D018180:Thrombomodulin; D004815:Epidermal Growth Factor