6owo

CRYO-EM STRUCTURE OF PHOSPHORYLATED AP-2 CORE BOUND TO NECAP

Loading... Status: waiting for Mol* initialization Structural highlights 6owo is a 5 chain structure with sequence from Mus musculus and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.2Å Ligands: TPO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Endocytosis of transmembrane proteins is orchestrated by the AP2 clathrin adaptor complex. AP2 dwells in a closed, inactive state in the cytosol, but adopts an open, active conformation on the plasma membrane. Membrane-activated complexes are also phosphorylated, but the significance of this mark is debated. We recently proposed that NECAP negatively regulates AP2 by binding open and phosphorylated complexes (Beacham et al., 2018). Here, we report high-resolution cryo-EM structures of NECAP bound to phosphorylated AP2. The site of AP2 phosphorylation is directly coordinated by residues of the NECAP PHear domain that are predicted from genetic screens in C. elegans. Using membrane mimetics to generate conformationally open AP2, we find that a second domain of NECAP binds these complexes and cryo-EM reveals both domains of NECAP engaging closed, inactive AP2. Assays in vitro and in vivo confirm these domains cooperate to inactivate AP2. We propose that phosphorylation marks adaptors for inactivation. A structural mechanism for phosphorylation-dependent inactivation of the AP2 complex.,Partlow EA, Baker RW, Beacham GM, Chappie JS, Leschziner AE, Hollopeter G Elife. 2019 Aug 29;8. pii: 50003. doi: 10.7554/eLife.50003. PMID:31464684 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Adaptin 3D structures

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