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SH3-III of Drosophila Rim-binding protein bound to a Cacophony derived peptideSH3-III of Drosophila Rim-binding protein bound to a Cacophony derived peptide
Structural highlights
FunctionPublication Abstract from PubMedSynaptic 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. A high affinity RIM-binding protein/Aplip1 interaction prevents the formation of ectopic axonal active zones.,Siebert M, Bohme MA, Driller JH, Babikir H, Mampell MM, Rey U, Ramesh N, Matkovic T, Holton N, Reddy-Alla S, Gottfert F, Kamin D, Quentin C, Klinedinst S, Andlauer TF, Hell SW, Collins CA, Wahl MC, Loll B, Sigrist SJ Elife. 2015 Aug 14;4. doi: 10.7554/eLife.06935. PMID:26274777[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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