6H5T

Intersectin SH3A short isoform

Summary for 6H5T

• Entry DOI: 10.2210/pdb6h5t/pdb
• Descriptor: Intersectin-1, 2,5,8,11,14,17,20,23-OCTAOXAPENTACOSAN-25-OL, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: sh3 domain, intersectin 1, splice isoform, endocytosis
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 22525.74

Authors

Driller, J.H.,Gerth, F.,Freund, C.,Wahl, M.C.,Loll, B. (deposition date: 2018-07-25, release date: 2019-02-27, Last modification date: 2024-05-15)

Primary citation

Gerth, F.,Japel, M.,Sticht, J.,Kuropka, B.,Schmitt, X.J.,Driller, J.H.,Loll, B.,Wahl, M.C.,Pagel, K.,Haucke, V.,Freund, C.
Exon Inclusion Modulates Conformational Plasticity and Autoinhibition of the Intersectin 1 SH3A Domain.
Structure, 27:977-, 2019

PubMed Abstract: 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 β 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.

PubMed: 31031201
DOI: 10.1016/j.str.2019.03.020

Experimental method

X-RAY DIFFRACTION (1.689 Å)