M. Hosaka et Tc. Sudhof, SYNAPSIN-I AND SYNAPSIN-II ARE ATP-BINDING PROTEINS WITH DIFFERENTIALCA2+ REGULATION, The Journal of biological chemistry, 273(3), 1998, pp. 1425-1429
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 conserve
d, large central domain, the C-domain, that accounts for the majority
of their sequences, Unexpectedly, the crystal structure of the C-domai
n 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., Sudhof, T. C., and Deisenh
ofer, 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 m
odules, The two C-domains exhibit similar ATP affinities but are diffe
rentially regulated; ATP binding to synapsin I is Ca2+-dependent where
as ATP binding to synapsin II, is Ca2+-independent, In synapsin I, the
Ca2+ requirement for ATP binding is mediated by a single, evolutionar
ily conserved glutamate residue (Glu(373)) at a position where synapsi
n II contains a lysine residue, Exchange of Glu(373) for lysine conver
ts synapsin I from a Ca2+-dependent protein into a Ca2+-independent AT
P-binding protein, Our studies suggest that synapsins I and II functio
n on synaptic vesicles as ATP-binding proteins that are differentially
regulated by Ca2+.