4Z89

SH3-II of Drosophila Rim-binding protein bound to a Cacophony derived peptide

Summary for 4Z89

• Entry DOI: 10.2210/pdb4z89/pdb
• Related: 2CSQ
• Descriptor: RIM-binding protein, isoform F, Voltage-dependent calcium channel type A subunit alpha-1, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: synapse, active zone, sh3 domain, rim-binding protein, cacophony peptide
• Biological source: Drosophila melanogaster (Fruit fly); More
• Cellular location: Membrane; Multi-pass membrane protein: P91645
• Total number of polymer chains: 20
• Total formula weight: 99280.20

Authors

Driller, J.H.,Holton, N.,Siebert, M.,Boehme, M.A.,Wahl, M.C.,Sigrist, S.J.,Loll, B. (deposition date: 2015-04-08, release date: 2015-08-05, Last modification date: 2024-11-13)

Primary citation

Siebert, M.,Bohme, M.A.,Driller, J.H.,Babikir, H.,Mampell, M.M.,Rey, U.,Ramesh, N.,Matkovic, T.,Holton, N.,Reddy-Alla, S.,Gottfert, F.,Kamin, D.,Quentin, C.,Klinedinst, S.,Andlauer, T.F.,Hell, S.W.,Collins, C.A.,Wahl, M.C.,Loll, B.,Sigrist, S.J.
A high affinity RIM-binding protein/Aplip1 interaction prevents the formation of ectopic axonal active zones.
Elife, 4:-, 2015

PubMed Abstract: Synaptic vesicles (SVs) fuse at active zones (AZs) covered by a protein scaffold, at Drosophila synapses comprised of ELKS family member Bruchpilot (BRP) and RIM-binding protein (RBP). We here demonstrate axonal co-transport of BRP and RBP using intravital live imaging, with both proteins co-accumulating in axonal aggregates of several transport mutants. RBP, via its C-terminal Src-homology 3 (SH3) domains, binds Aplip1/JIP1, a transport adaptor involved in kinesin-dependent SV transport. We show in atomic detail that RBP C-terminal SH3 domains bind a proline-rich (PxxP) motif of Aplip1/JIP1 with submicromolar affinity. Pointmutating this PxxP motif provoked formation of ectopic AZ-like structures at axonal membranes. Direct interactions between AZ proteins and transport adaptors seem to provide complex avidity and shield synaptic interaction surfaces of pre-assembled scaffold protein transport complexes, thus, favouring physiological synaptic AZ assembly over premature assembly at axonal membranes.

PubMed: 26274777
DOI: 10.7554/eLife.06935

Experimental method

X-RAY DIFFRACTION (2.64 Å)