2VJ0

Crystal structure of the alpha-adaptin appendage domain, from the AP2 adaptor complex, in complex with an FXDNF peptide from amphiphysin1 and a WVXF peptide from synaptojanin P170

Summary for 2VJ0

• Entry DOI: 10.2210/pdb2vj0/pdb
• Related: 1B9K 1GW5 1KY6 1KY7 1KYF 1KYU 1QTP 1QTS 1W80 2DNR
• Descriptor: AP-2 COMPLEX SUBUNIT ALPHA-2, SYNAPTOJANIN-1, AMPHIPHYSIN, ... (8 entities in total)
• Functional Keywords: protein transport, cytoplasmic vesicle, alternative splicing, transport, coated pit, sh3 domain, endocytosis, alpha-adaptin, golgi apparatus, phosphorylation, ap2, synapse, membrane, cytoplasm, coiled coil, amphiphysin, cytoskeleton, synaptojanin, lipid-binding, cell junction
• Biological source: MUS MUSCULUS (MOUSE); More
• Cellular location: Cell membrane: P17427; Cytoplasm (By similarity): O43426; Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane; Peripheral membrane protein; Cytoplasmic side (By similarity): O08838
• Total number of polymer chains: 3
• Total formula weight: 30976.45

Authors

Ford, M.G.J.,Praefcke, G.J.K.,McMahon, H.T. (deposition date: 2007-12-06, release date: 2007-12-25, Last modification date: 2023-12-13)

Primary citation

Olesen, L.E.,Ford, M.G.J.,Schmid, E.M.,Vallis, Y.,Madan Babu, M.,Li, P.H.,Mills, I.G.,Mcmahon, H.T.,Praefcke, G.J.K.
Solitary and Repetitive Binding Motifs for the Ap2 Complex {Alpha}-Appendage in Amphiphysin and Other Accessory Proteins.
J.Biol.Chem., 283:5099-, 2008

PubMed Abstract: Adaptor protein (AP) complexes bind to transmembrane proteins destined for internalization and to membrane lipids, so linking cargo to the accessory internalization machinery. This machinery interacts with the appendage domains of APs, which have platform and beta-sandwich subdomains, forming the binding surfaces for interacting proteins. Proteins that interact with the subdomains do so via short motifs, usually found in regions of low structural complexity of the interacting proteins. So far, up to four motifs have been identified that bind to and partially compete for at least two sites on each of the appendage domains of the AP2 complex. Motifs in individual accessory proteins, their sequential arrangement into motif domains, and partial competition for binding sites on the appendage domains coordinate the formation of endocytic complexes in a temporal and spatial manner. In this work, we examine the dominant interaction sequence in amphiphysin, a synapse-enriched accessory protein, which generates membrane curvature and recruits the scission protein dynamin to the necks of coated pits, for the platform subdomain of the alpha-appendage. The motif domain of amphiphysin1 contains one copy of each of a DX(F/W) and FXDXF motif. We find that the FXDXF motif is the main determinant for the high affinity interaction with the alpha-adaptin appendage. We describe the optimal sequence of the FXDXF motif using thermodynamic and structural data and show how sequence variation controls the affinities of these motifs for the alpha-appendage.

PubMed: 17986441
DOI: 10.1074/JBC.M708621200

Experimental method

X-RAY DIFFRACTION (1.6 Å)