7oi5

Structural highlights

Function

AP2M1_RAT Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. The AP-2 mu subunit binds to transmembrane cargo proteins; it recognizes the Y-X-X-Phi motifs. The surface region interacting with to the Y-X-X-Phi motif is inaccessible in cytosolic AP-2, but becomes accessible through a conformational change following phosphorylation of AP-2 mu subunit at 'Tyr-156' in membrane-associated AP-2. The membrane-specific phosphorylation event appears to involve assembled clathrin which activates the AP-2 mu kinase AAK1 (By similarity). Plays a role in endocytosis of frizzled family members upon Wnt signaling.^{[1] [2] [3] [4]} FCHO2_HUMAN Functions in an early step of clathrin-mediated endocytosis. Has both a membrane binding/bending activity and the ability to recruit proteins essential to the formation of functional clathrin-coated pits. Has a lipid-binding activity with a preference for membranes enriched in phosphatidylserine and phosphoinositides (Pi(4,5) biphosphate) like the plasma membrane. Its membrane-bending activity might be important for the subsequent action of clathrin and adaptors in the formation of clathrin-coated vesicles. Involved in adaptor protein complex AP-2-dependent endocytosis of the transferrin receptor, it also functions in the AP-2-independent endocytosis of the LDL receptor.^{[5] [6] [7] [8]}

See Also

• Adaptin 3D structures

References

1. ↑ Olusanya O, Andrews PD, Swedlow JR, Smythe E. Phosphorylation of threonine 156 of the mu2 subunit of the AP2 complex is essential for endocytosis in vitro and in vivo. Curr Biol. 2001 Jun 5;11(11):896-900. PMID:11516654
2. ↑ Nakatsu F, Ohno H. Adaptor protein complexes as the key regulators of protein sorting in the post-Golgi network. Cell Struct Funct. 2003 Oct;28(5):419-29. PMID:14745134
3. ↑ Owen DJ, Collins BM, Evans PR. Adaptors for clathrin coats: structure and function. Annu Rev Cell Dev Biol. 2004;20:153-91. PMID:15473838 doi:10.1146/annurev.cellbio.20.010403.104543
4. ↑ Yu A, Xing Y, Harrison SC, Kirchhausen T. Structural analysis of the interaction between Dishevelled2 and clathrin AP-2 adaptor, a critical step in noncanonical Wnt signaling. Structure. 2010 Oct 13;18(10):1311-20. PMID:20947020 doi:10.1016/j.str.2010.07.010
5. ↑ Henne WM, Kent HM, Ford MG, Hegde BG, Daumke O, Butler PJ, Mittal R, Langen R, Evans PR, McMahon HT. Structure and analysis of FCHo2 F-BAR domain: a dimerizing and membrane recruitment module that effects membrane curvature. Structure. 2007 Jul;15(7):839-52. Epub 2007 Jun 1. PMID:17540576 doi:10.1016/j.str.2007.05.002
6. ↑ Henne WM, Boucrot E, Meinecke M, Evergren E, Vallis Y, Mittal R, McMahon HT. FCHo proteins are nucleators of clathrin-mediated endocytosis. Science. 2010 Jun 4;328(5983):1281-4. PMID:20448150 doi:10.1126/science.1188462
7. ↑ Uezu A, Umeda K, Tsujita K, Suetsugu S, Takenawa T, Nakanishi H. Characterization of the EFC/F-BAR domain protein, FCHO2. Genes Cells. 2011 Aug;16(8):868-78. PMID:21762413 doi:10.1111/j.1365-2443.2011.01536.x
8. ↑ Mulkearns EE, Cooper JA. FCH domain only-2 organizes clathrin-coated structures and interacts with Disabled-2 for low-density lipoprotein receptor endocytosis. Mol Biol Cell. 2012 Apr;23(7):1330-42. doi: 10.1091/mbc.E11-09-0812. Epub 2012, Feb 9. PMID:22323290 doi:http://dx.doi.org/10.1091/mbc.E11-09-0812