| Structural highlights
4hmy is a 5 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| Gene: | Adtg, Ap1g1, Clapg1 (LK3 transgenic mice), ADTB1, AP1B1, BAM22, CLAPB2 (HUMAN), Ap1m1, Cltnm (LK3 transgenic mice), AP1S3 (HUMAN), ARF1 (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
[AP1S3_HUMAN] Acrodermatitis continua suppurativa of Hallopeau;Generalized pustular psoriasis;Pustulosis palmaris et plantaris. Disease susceptibility is associated with variations affecting the gene represented in this entry.
Function
[AP1S3_HUMAN] Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules. Involved in TLR3 trafficking (PubMed:24791904).[1] [AP1G1_MOUSE] Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules. [AP1M1_MOUSE] Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the trans-Golgi network (TGN) and endosomes. The AP complexes mediate the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules. [AP1B1_HUMAN] Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules. [ARF1_HUMAN] GTP-binding protein that functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase. Involved in protein trafficking among different compartments. Modulates vesicle budding and uncoating within the Golgi complex. Deactivation induces the redistribution of the entire Golgi complex to the endoplasmic reticulum, suggesting a crucial role in protein trafficking. In its GTP-bound form, its triggers the association with coat proteins with the Golgi membrane. The hydrolysis of ARF1-bound GTP, which is mediated by ARFGAPs proteins, is required for dissociation of coat proteins from Golgi membranes and vesicles.
Publication Abstract from PubMed
AP-1 is a clathrin adaptor complex that sorts cargo between the trans-Golgi network and endosomes. AP-1 recruitment to these compartments requires Arf1-GTP. The crystal structure of the tetrameric core of AP-1 in complex with Arf1-GTP, together with biochemical analyses, shows that Arf1 activates cargo binding by unlocking AP-1. Unlocking is driven by two molecules of Arf1 that bridge two copies of AP-1 at two interaction sites. The GTP-dependent switch I and II regions of Arf1 bind to the N terminus of the beta1 subunit of one AP-1 complex, while the back side of Arf1 binds to the central part of the gamma subunit trunk of a second AP-1 complex. A third Arf1 interaction site near the N terminus of the gamma subunit is important for recruitment, but not activation. These observations lead to a model for the recruitment and activation of AP-1 by Arf1.
Structural Basis for Recruitment and Activation of the AP-1 Clathrin Adaptor Complex by Arf1.,Ren X, Farias GG, Canagarajah BJ, Bonifacino JS, Hurley JH Cell. 2013 Feb 14;152(4):755-67. doi: 10.1016/j.cell.2012.12.042. PMID:23415225[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Setta-Kaffetzi N, Simpson MA, Navarini AA, Patel VM, Lu HC, Allen MH, Duckworth M, Bachelez H, Burden AD, Choon SE, Griffiths CE, Kirby B, Kolios A, Seyger MM, Prins C, Smahi A, Trembath RC, Fraternali F, Smith CH, Barker JN, Capon F. AP1S3 mutations are associated with pustular psoriasis and impaired Toll-like receptor 3 trafficking. Am J Hum Genet. 2014 May 1;94(5):790-7. doi: 10.1016/j.ajhg.2014.04.005. PMID:24791904 doi:http://dx.doi.org/10.1016/j.ajhg.2014.04.005
- ↑ Ren X, Farias GG, Canagarajah BJ, Bonifacino JS, Hurley JH. Structural Basis for Recruitment and Activation of the AP-1 Clathrin Adaptor Complex by Arf1. Cell. 2013 Feb 14;152(4):755-67. doi: 10.1016/j.cell.2012.12.042. PMID:23415225 doi:http://dx.doi.org/10.1016/j.cell.2012.12.042
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