title: Structure of the Janus-faced C2B domain of rabphilin.
abstract: C2 domains are widespread protein modules that often occur as tandem repeats in many membrane-trafficking proteins such as synaptotagmin and rabphilin. The first and second C2 domains (C2A and C2B, respectively) have a high degree of homology but also specific differences. The structure of the C2A domain of synaptotagmin I has been extensively studied but little is known about the C2B domains. We have used NMR spectroscopy to determine the solution structure of the C2B domain of rabphilin. The overall structure of the C2B domain is very similar to that of other C2 domains, with a rigid beta-sandwich core and loops at the top (where Ca2+ binds) and the bottom. Surprisingly, a relatively long alpha-helix is inserted at the bottom of the domain and is conserved in all C2B domains. Our results, together with the Ca(2+)-independent interactions observed for C2B domains, indicate that these domains have a Janus-faced nature, with a Ca(2+)-binding top surface and a Ca(2+)-independent bottom surface.
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235, USA.
authors.forename: J
authors.initials: J
authors.lastname: Ubach
authors.forename: J
authors.initials: J
authors.lastname: García
authors.forename: M P
authors.initials: MP
authors.lastname: Nittler
authors.forename: T C
authors.initials: TC
authors.lastname: Südhof
authors.forename: J
authors.initials: J
authors.lastname: Rizo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002135:Calcium-Binding Proteins / Q000737:chemistry; D017124:Conserved Sequence; D008562:Membrane Glycoproteins / Q000737:chemistry; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D017433:Protein Structure, Secondary; D051381:Rats; D020449:Repetitive Sequences, Amino Acid; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013050:Spectrometry, Fluorescence / Q000379:methods; D050863:Synaptotagmin I; D050857:Synaptotagmins; D033921:Vesicular Transport Proteins; D020691:rab GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D000097624:Rabphilin-3A
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D050863:Synaptotagmin I; D050857:Synaptotagmins; D033921:Vesicular Transport Proteins; D020691:rab GTP-Binding Proteins; D000097624:Rabphilin-3A; C494311:Syt1 protein, mouse; C494312:Syt1 protein, rat