RIM p
roteins play c
ritical
roles in synaptic vesicle p
riming and dive
rse fo
rms of p
resynapticplasticity. The C-te
rminal C
2B domain is the only module that is common to all RIMs but is only distantly
related to well-studied C
2 domains, and its th
ree-dimensional st
ructu
re and inte
ractions have not beencha
racte
rized in detail. Using NMR spect
roscopy, we now show that N- and C-te
rminal extensions beyondthe p
redicted C
2B domain co
re sequence a
re necessa
ry to fo
rm a folded, stable RIM1
rs/alpha.gif" BORDER=0> C
2B domain. Wealso find that the isolated RIM1
rs/alpha.gif" BORDER=0> C
2B domain is not sufficient fo
r p
reviously desc
ribed p
rotein-p
roteininte
ractions involving the RIM1
rs/alpha.gif" BORDER=0> C-te
rminus, suggesting that additional sequences adjacent to the C
2Bdomain might be
requi
red fo
r these inte
ractions. Howeve
r, analytical ult
racent
rifugation shows that theRIM1
rs/alpha.gif" BORDER=0> C
2B domain fo
rms weak dime
rs in solution. The c
rystal st
ructu
re of the RIM1
rs/alpha.gif" BORDER=0> C
2B domaindime
r at 1.7 &A
ring;
resolution
reveals that it fo
rms a
rs/beta2.gif" BORDER=0 ALIGN="middle">-sandwich cha
racte
ristic of C
2 domains and that theunique N- and C-te
rminal extensions fo
rm a small subdomain that packs against the
rs/beta2.gif" BORDER=0 ALIGN="middle">-sandwich andmediates dime
rization. Ou
r results p
rovide a st
ructu
ral basis to unde
rstand the function of RIM C
2B domainsand suggest that dime
rization may be a c
rucial aspect of RIM function.