2K3H

Structural determinants for Ca2+ and PIP2 binding by the C2A domain of rabphilin-3A

Summary for 2K3H

• Entry DOI: 10.2210/pdb2k3h/pdb
• Descriptor: Rabphilin-3A, CALCIUM ION (2 entities in total)
• Functional Keywords: pip2, c2 domain, calcium, tama mechanism, cell junction, metal-binding, phosphoprotein, protein transport, synapse, transport, zinc, zinc-finger
• Biological source: Mus musculus (mouse)
• Cellular location: Cell junction, synapse (By similarity): P47708
• Total number of polymer chains: 1
• Total formula weight: 16153.33

Authors

Coudevylle, N.,Montaville, P.,Leonov, A.,Zweckstetter, M.,Becker, S. (deposition date: 2008-05-08, release date: 2008-10-21, Last modification date: 2024-05-29)

Primary citation

Coudevylle, N.,Montaville, P.,Leonov, A.,Zweckstetter, M.,Becker, S.
Structural Determinants for Ca2+ and Phosphatidylinositol 4,5-Bisphosphate Binding by the C2A Domain of Rabphilin-3A.
J.Biol.Chem., 283:35918-35928, 2008

PubMed Abstract: Rabphilin-3A is a neuronal C2 domain tandem containing protein involved in vesicle trafficking. Both its C2 domains (C2A and C2B) are able to bind phosphatidylinositol 4,5-bisphosphate, a key player in the neurotransmitter release process. The rabphilin-3A C2A domain has previously been shown to bind inositol-1,4,5-trisphosphate (IP3; phosphatidylinositol 4,5-bisphosphate headgroup) in a Ca2+-dependent manner with a relatively high affinity (50 microm) in the presence of saturating concentrations of Ca2+. Moreover, IP3 and Ca2+ binding to the C2A domain mutually enhance each other. Here we present the Ca2+-bound solution structure of the C2A domain. Structural comparison with the previously published Ca2+-free crystal structure revealed that Ca2+ binding induces a conformational change of Ca2+ binding loop 3 (CBL3). Our IP3 binding studies as well as our IP3-C2A docking model show the active involvement of CBL3 in IP3 binding, suggesting that the conformational change on CBL3 upon Ca2+ binding enables the interaction with IP3 and vice versa, in line with a target-activated messenger affinity mechanism. Our data provide detailed structural insight into the functional properties of the rabphilin-3A C2A domain and reveal for the first time the structural determinants of a target-activated messenger affinity mechanism.

PubMed: 18945677
DOI: 10.1074/jbc.M804094200

Experimental method

SOLUTION NMR