| First Author | Gerth F | Year | 2019 |
| Journal | Structure | Volume | 27 |
| Issue | 6 | Pages | 977-987.e5 |
| PubMed ID | 31031201 | Mgi Jnum | J:289199 |
| Mgi Id | MGI:6434660 | Doi | 10.1016/j.str.2019.03.020 |
| Citation | Gerth F, et al. (2019) Exon Inclusion Modulates Conformational Plasticity and Autoinhibition of the Intersectin 1 SH3A Domain. Structure 27(6):977-987.e5 |
| abstractText | 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. |
