title: Tertiary structure of human complement component C5a in solution from nuclear magnetic resonance data.
abstract: The tertiary structure for the region 1-63 of the 74 amino acid human complement protein C5a in solution was calculated from a large number of distance constraints derived from nuclear Overhauser effects with an angular distance geometry algorithm. The protein consists of four helices juxtaposed in an approximately antiparallel topology connected by peptide loops located at the surface of the molecule. The structures obtained for the helices are compatible with alpha-helical hydrogen-bonding patterns, which provides an explanation for the observed slow solvent exchange kinetics of the amide protons in these peptide regions. In contrast to the peptide region 1-63, no defined structure could be assigned to the C-terminal region 64-74, which increasingly acquires dynamic random coil characteristics as the end of the peptide chain is approached. An average root-mean-square deviation of 1.6 A was obtained for the alpha-carbons of the first 63 residues in the calculated ensemble of C5a structures, while the alpha-helices were determined with an average root-mean-square deviation of 0.8 A for the alpha-carbons. A comparison between the solution structure of C5a and the crystal structure of the functionally related C3a protein, as well as inferences for the interaction of C5a with its receptor on polymorphonuclear leukocytes, is discussed.
authors: Research NMR Group, Abbott Laboratories, Abbott Park, Illinois 60064.
authors: E R
authors: ER
authors: Zuiderweg
authors: D G
authors: DG
authors: Nettesheim
authors: K W
authors: KW
authors: Mollison
authors: G W
authors: GW
authors: Carter
mesh_terms: D000595:Amino Acid Sequence; D003176:Complement C3; D015926:Complement C3a; D003182:Complement C5 / Q000502:physiology; D015936:Complement C5a; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010446:Peptide Fragments; D011487:Protein Conformation; D012996:Solutions; D013329:Structure-Activity Relationship
chemical_list: D003176:Complement C3; D003182:Complement C5; D010446:Peptide Fragments; D012996:Solutions; D015926:Complement C3a; D015936:Complement C5a