title: Structure of the C2A domain of rabphilin-3A.
abstract: Rabphilin-3A is a neuronal protein containing a C2-domain tandem. To date, only the structure of the C2B domain has been solved. The crystal structure of the Ca2+-free C2A domain has been solved by molecular replacement and refined to 1.92 A resolution. It adopts the classical C2-domain fold consisting of an eight-stranded antiparallel beta-sandwich with type I topology. In agreement with its Ca2+-dependent negatively charged membrane-binding properties, this C2 domain contains all the conserved acidic residues responsible for calcium binding. However, the replacement of a conserved aspartic acid residue by glutamic acid allows formation of an additional strong hydrogen bond, resulting in increased rigidity of calcium-binding loop 1. The electrostatic surface of the C2A domain consists of a large positively charged belt surrounded by two negatively charged patches located at both tips of the domain. In comparison, the structurally very similar C2A domain of synaptotagmin I has a highly acidic electrostatic surface, suggesting completely unrelated functions for these two C2A domains.
authors.affiliation: Department of Structural Chemistry, University of Göttingen, Tammanstrasse 4, 37077 Göttingen, Germany.
authors.forename: Marianna
authors.initials: M
authors.lastname: Biadene
authors.forename: Pierre
authors.initials: P
authors.lastname: Montaville
authors.forename: George M
authors.initials: GM
authors.lastname: Sheldrick
authors.forename: Stefan
authors.initials: S
authors.lastname: Becker
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D003460:Crystallization; D018360:Crystallography, X-Ray / Q000379:methods*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051381:Rats; D017386:Sequence Homology, Amino Acid; D033921:Vesicular Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000097624:Rabphilin-3A
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002118:Calcium; D002135:Calcium-Binding Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D033921:Vesicular Transport Proteins; D000097624:Rabphilin-3A