3HS8

Intersectin 1-peptide-AP2 alpha ear complex

Summary for 3HS8

• Entry DOI: 10.2210/pdb3hs8/pdb
• Related: 3HS9
• Descriptor: Adaptor protein complex AP-2, alpha 2 subunit, peptide from Intersectin-1, residues 840-851 (3 entities in total)
• Functional Keywords: adaptor complex ap-2, endocytosis, cell membrane, coated pit, lipid-binding, membrane, disease mutation, transferase
• Biological source: Mus musculus (mouse); More
• Cellular location: Cytoplasm : Q6PEE6; Endomembrane system : Q9Z0R4
• Total number of polymer chains: 2
• Total formula weight: 32166.36

Authors

Vahedi-Faridi, A.,Pechstein, A.,Schaefer, J.G.,Saenger, W.,Haucke, V. (deposition date: 2009-06-10, release date: 2010-02-23, Last modification date: 2024-03-20)

Primary citation

Pechstein, A.,Bacetic, J.,Vahedi-Faridi, A.,Gromova, K.,Sundborger, A.,Tomlin, N.,Krainer, G.,Vorontsova, O.,Schafer, J.G.,Owe, S.G.,Cousin, M.A.,Saenger, W.,Shupliakov, O.,Haucke, V.
Regulation of synaptic vesicle recycling by complex formation between intersectin 1 and the clathrin adaptor complex AP2.
Proc.Natl.Acad.Sci.USA, 107:4206-4211, 2010

PubMed Abstract: Clathrin-mediated synaptic vesicle (SV) recycling involves the spatiotemporally controlled assembly of clathrin coat components at phosphatidylinositiol (4, 5)-bisphosphate [PI(4,5)P(2)]-enriched membrane sites within the periactive zone. Such spatiotemporal control is needed to coordinate SV cargo sorting with clathrin/AP2 recruitment and to restrain membrane fission and synaptojanin-mediated uncoating until membrane deformation and clathrin coat assembly are completed. The molecular events underlying these control mechanisms are unknown. Here we show that the endocytic SH3 domain-containing accessory protein intersectin 1 scaffolds the endocytic process by directly associating with the clathrin adaptor AP2. Acute perturbation of the intersectin 1-AP2 interaction in lamprey synapses in situ inhibits the onset of SV recycling. Structurally, complex formation can be attributed to the direct association of hydrophobic peptides within the intersectin 1 SH3A-B linker region with the "side sites" of the AP2 alpha- and beta-appendage domains. AP2 appendage association of the SH3A-B linker region inhibits binding of the inositol phosphatase synaptojanin 1 to intersectin 1. These data identify the intersectin-AP2 complex as an important regulator of clathrin-mediated SV recycling in synapses.

PubMed: 20160082
DOI: 10.1073/pnas.0911073107

Experimental method

X-RAY DIFFRACTION (1.9 Å)