6h5t

Publication Abstract from PubMed

The scaffolding protein intersectin 1 plays important roles in clathrin-mediated endocytosis and in the replenishment of release-ready synaptic vesicles (SV). Two splice variants of intersectin's SH3A domain are expressed in the brain, and association of the neuron-specific variant with synapsin I has been shown to enable sustained neurotransmission and to be regulated by an adjacent C-terminal motif. Here, we demonstrate that the ubiquitously expressed short SH3A variant of intersectin 1 interacts with an N-terminal intramolecular sequence that operates synergistically with the C-terminal motif. NMR spectroscopic investigations show that the five-amino acid insertion into the beta strand 2 of the neuronal SH3A variant introduces conformational plasticity incompatible with binding of the N-terminal sequence. The difference in the autoregulatory mechanism of the domain's variants differentially affects its synaptic binding partners, thereby establishing alternative splicing in conjunction with autoinhibitory motif variation as a mechanism to regulate protein interaction networks.

Exon Inclusion Modulates Conformational Plasticity and Autoinhibition of the Intersectin 1 SH3A Domain.,Gerth F, Japel M, Sticht J, Kuropka B, Schmitt XJ, Driller JH, Loll B, Wahl MC, Pagel K, Haucke V, Freund C Structure. 2019 Apr 9. pii: S0969-2126(19)30116-9. doi:, 10.1016/j.str.2019.03.020. PMID:31031201^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.