Synapsins I and II are ATP-binding proteins with differential Ca2+ regulation.
Synapsins I and II are abundant phosphoproteins that are localized to synaptic vesicles and have essential functions in regulating synaptic vesicle exocytosis. Synapsins contain a single evolutionarily conserved, large central domain, the C-domain, that accounts for the majority of their sequences. Unexpectedly, the crystal structure of the C-domain from synapsin I revealed that it is structurally closely related to several ATPases despite the absence of sequence similarities (Esser, L., Wang, C.-R., Hosaka, M., Smagula, C. S., Südhof, T. C., and Deisenhofer, J. (1998) EMBO J., in press). We now show that the C-domains of both synapsin I and synapsin II constitute high affinity ATP-binding modules. The two C-domains exhibit similar ATP affinities but are differentially regulated; ATP binding to synapsin I is Ca(2+)-dependent whereas ATP binding to synapsin II is Ca(2+)-independent. In synapsin I, the Ca2+ requirement for ATP binding is mediated by a single, evolutionarily conserved glutamate residue (Glu373) at a position where synapsin II contains a lysine residue. Exchange of Glu373 for lysine converts synapsin I from a Ca(2+)-dependent protein into a Ca(2+)-independent ATP-binding protein. Our studies suggest that synapsins I and II function on synaptic vesicles as ATP-binding proteins that are differentially regulated by Ca2+.
Hosaka
M
M
Howard Hughes Medical Institute, University of Texas Southwestern Medical School, Dallas 75235, USA. TSudho@mednet.swmed.edu
Südhof
T C
TC
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000378:metabolism; D016704:Synapsins / Q000378:metabolism*
D011994:Recombinant Proteins; D016704:Synapsins; C022571:adenosine 5'-O-(3-thiotriphosphate); D000255:Adenosine Triphosphate; D002118:Calcium