Protein Science, Vol 1, Issue 1 81-90, Copyright © 1992 by Cold Spring Harbor Laboratory Press

ARTICLE

The three-dimensional structure of the first EGF-like module of human factor IX: Comparison with EGF and TGF-{alpha}

M. BARON, D. G. NORMAN, T. S. HARVEY, P. A. HANDFORD, M. MAYHEW, AGG. TSE, G. G. BROWNLEE and I. D. CAMPBELL
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK

The three-dimensional structure of the first epidermal growth factor (EGF)-like module from human factor IX has been determined in solution using two-dimensional nuclear magnetic resonance (in the absence of calcium and at pH 4.5). The structure was found to resemble closely that of EGF and the homologous transforming growth factor-{alpha} (TGF-{alpha}). Residues 60-65 form an antiparallel {beta}-sheet with residues 68-73. In the C-terminal subdomain a type II {beta}-turn is found between residues 74 and 77 and a five-residue turn is found between residues 79 and 83. Glu 78 and Leu 84 pair in an antiparallel {beta}-sheet conformation. In the N-terminal region a loop is found between residues 50 and 55 such that the side chains of both are positioned above the face of the {beta}-sheet. Residues 56-60 form a turn that leads into the first strand of the {beta}-sheet. Whereas the global fold closely resembles that of EGF, the N-terminal residues of the module (46-49) do not form a {beta}-strand but are ill-defined in the structure, probably due to the local flexibility of this region. The structure is discussed with reference to recent site-directed mutagenesis data, which have identified certain conserved residues as ligands for calcium.
CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?