title: The structure of a Ca(2+)-binding epidermal growth factor-like domain: its role in protein-protein interactions.
abstract: Various diverse extracellular proteins possess Ca(2+)-binding epidermal growth factor (EGF)-like domains, the function of which remains uncertain. We have determined, at high resolution (1.5 A), the crystal structure of such a domain, from human clotting factor IX, as a complex with Ca2+. The Ca2+ ligands form a classic pentagonal bipyramid with six ligands contributed by one polypeptide chain and the seventh supplied by a neighboring EGF-like domain. The crystal structure identifies the role of Ca2+ in maintaining the conformation of the N-terminal region of the domain, but more importantly demonstrates that Ca2+ can directly mediate protein-protein contacts. The observed crystal packing of the domains provides a plausible model for the association of multiple tandemly linked EGF-like domains in proteins such as fibrillin-1, Notch, and protein S. This model is consistent with the known functional data and suggests a general biological role for these domains.
authors.affiliation: Laboratory of Molecular Biophysics, University of Oxford, England.
authors.forename: Z
authors.initials: Z
authors.lastname: Rao
authors.forename: P
authors.initials: P
authors.lastname: Handford
authors.forename: M
authors.initials: M
authors.lastname: Mayhew
authors.forename: V
authors.initials: V
authors.lastname: Knott
authors.forename: G G
authors.initials: GG
authors.lastname: Brownlee
authors.forename: D
authors.initials: D
authors.lastname: Stuart
mesh_terms: D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism*; D003196:Computer Graphics; D018360:Crystallography, X-Ray; D004815:Epidermal Growth Factor / Q000737:chemistry* / Q000378:metabolism; D005164:Factor IX / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D016415:Sequence Alignment
chemical_list: D004815:Epidermal Growth Factor; D005164:Factor IX; D002118:Calcium