Structure of the first C2 domain of synaptotagmin I: a novel Ca2+/phospholipid-binding fold.
C2 domains are regulatory sequence motifs that occur widely in nature. Synaptotagmin I, a synaptic vesicle protein involved in the Ca2+ regulation of exocytosis, contains two C2 domains, the first of which acts as a Ca2+ sensor. We now describe the three-dimensional structure of this C2 domain at 1.9 A resolution in both the Ca(2+)-bound and Ca(2+)-free forms. The C2 polypeptide forms an eight-stranded beta sandwich constructed around a conserved four-stranded motif designated as a C2 key. Ca2+ binds in a cup-shaped depression between two polypeptide loops located at the N- and C-termini of the C2-key motif.
Sutton
R B
RB
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235.
Davletov
B A
BA
Berghuis
A M
AM
Südhof
T C
TC
Sprang
S R
SR
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D017124:Conserved Sequence; D005089:Exocytosis; D008081:Liposomes; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides; D010713:Phosphatidylcholines / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013572:Synaptic Vesicles / Q000378:metabolism; D050863:Synaptotagmin I; D050857:Synaptotagmins
D002135:Calcium-Binding Proteins; D008081:Liposomes; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D009838:Oligodeoxyribonucleotides; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D010743:Phospholipids; D011994:Recombinant Proteins; D050863:Synaptotagmin I; D050857:Synaptotagmins; D002118:Calcium