6h5t | pdb_00006h5t

Intersectin SH3A short isoform

spinqualitylabelsall models 6h5t, resolution 1.69Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6h5t is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 7PG, ACT, CL, ZN Gene: ITSN1, ITSN, SH3D1A (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ITSN1_HUMAN] Adapter protein that may provide indirect link between the endocytic membrane traffic and the actin assembly machinery. May regulate the formation of clathrin-coated vesicles. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR may involve association with DAB2. Isoform 1 could be involved in brain-specific synaptic vesicle recycling. Inhibits ARHGAP31 activity toward RAC1. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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