6RH5

Solution structure and 1H, 13C and 15N chemical shift assignments for NECAP1 PHear domain

Summary for 6RH5

• Entry DOI: 10.2210/pdb6rh5/pdb
• NMR Information: BMRB: 34394
• Descriptor: Adaptin ear-binding coat-associated protein 1 (1 entity in total)
• Functional Keywords: clathrin mediated endocytosis, regulation by phosphorylation, ap2 endocytic adaptor, necap snx9, endocytosis
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 15562.37

Authors

Owen, D.J.,Neuhaus, D.,Yang, J.-C.,Herrmann, T. (deposition date: 2019-04-18, release date: 2019-09-04, Last modification date: 2024-05-15)

Primary citation

Wrobel, A.G.,Kadlecova, Z.,Kamenicky, J.,Yang, J.C.,Herrmann, T.,Kelly, B.T.,McCoy, A.J.,Evans, P.R.,Martin, S.,Muller, S.,Sroubek, F.,Neuhaus, D.,Honing, S.,Owen, D.J.
Temporal Ordering in Endocytic Clathrin-Coated Vesicle Formation via AP2 Phosphorylation.
Dev.Cell, 50:494-508.e11, 2019

PubMed Abstract: Clathrin-mediated endocytosis (CME) is key to maintaining the transmembrane protein composition of cells' limiting membranes. During mammalian CME, a reversible phosphorylation event occurs on Thr156 of the μ2 subunit of the main endocytic clathrin adaptor, AP2. We show that this phosphorylation event starts during clathrin-coated pit (CCP) initiation and increases throughout CCP lifetime. μ2Thr156 phosphorylation favors a new, cargo-bound conformation of AP2 and simultaneously creates a binding platform for the endocytic NECAP proteins but without significantly altering AP2's cargo affinity in vitro. We describe the structural bases of both. NECAP arrival at CCPs parallels that of clathrin and increases with μ2Thr156 phosphorylation. In turn, NECAP recruits drivers of late stages of CCP formation, including SNX9, via a site distinct from where NECAP binds AP2. Disruption of the different modules of this phosphorylation-based temporal regulatory system results in CCP maturation being delayed and/or stalled, hence impairing global rates of CME.

PubMed: 31430451
DOI: 10.1016/j.devcel.2019.07.017

Experimental method

SOLUTION NMR