| Structural highlights
Function
[PTN23_HUMAN] Plays a role in sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs) via its interaction with the ESCRT-I complex (endosomal sorting complex required for transport I), and possibly also other ESCRT complexes. May act as a negative regulator of Ras-mediated mitogenic activity. Plays a role in ciliogenesis.[1] [2] [3]
Publication Abstract from PubMed
Alix and cellular paralogs HD-PTP and Brox contain N-terminal Bro1 domains that bind ESCRT-III CHMP4. In contrast to HD-PTP and Brox, expression of the Bro1 domain of Alix alleviates HIV-1 release defects as a result of interrupted access to ESCRT. In an attempt to elucidate this functional discrepancy, we solved the crystal structures of the Bro1 domains of HD-PTP and Brox. They revealed typical "boomerang" folds they share with the Bro1 Alix domain. However, they each contain unique structural features that may be relevant to their specific function(s). In particular, phenylalanine residue in position 105 (Phe105) of Alix belongs to a long loop that is unique to its Bro1 domain. Concurrently, mutation of Phe105 and surrounding residues at the tip of the loop compromise the function of Alix in HIV-1 budding without affecting its interactions with Gag or CHMP4. These studies identify a functional determinant in the Bro1 domain of Alix.
The Phe105 Loop of Alix Bro1 Domain Plays a Key Role in HIV-1 Release.,Sette P, Mu R, Dussupt V, Jiang J, Snyder G, Smith P, Xiao TS, Bouamr F Structure. 2011 Sep 1. PMID:21889351[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Doyotte A, Mironov A, McKenzie E, Woodman P. The Bro1-related protein HD-PTP/PTPN23 is required for endosomal cargo sorting and multivesicular body morphogenesis. Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6308-13. doi:, 10.1073/pnas.0707601105. Epub 2008 Apr 23. PMID:18434552 doi:http://dx.doi.org/10.1073/pnas.0707601105
- ↑ Kim J, Lee JE, Heynen-Genel S, Suyama E, Ono K, Lee K, Ideker T, Aza-Blanc P, Gleeson JG. Functional genomic screen for modulators of ciliogenesis and cilium length. Nature. 2010 Apr 15;464(7291):1048-51. doi: 10.1038/nature08895. PMID:20393563 doi:10.1038/nature08895
- ↑ Stefani F, Zhang L, Taylor S, Donovan J, Rollinson S, Doyotte A, Brownhill K, Bennion J, Pickering-Brown S, Woodman P. UBAP1 is a component of an endosome-specific ESCRT-I complex that is essential for MVB sorting. Curr Biol. 2011 Jul 26;21(14):1245-50. doi: 10.1016/j.cub.2011.06.028. Epub 2011 , Jul 14. PMID:21757351 doi:http://dx.doi.org/10.1016/j.cub.2011.06.028
- ↑ Sette P, Mu R, Dussupt V, Jiang J, Snyder G, Smith P, Xiao TS, Bouamr F. The Phe105 Loop of Alix Bro1 Domain Plays a Key Role in HIV-1 Release. Structure. 2011 Sep 1. PMID:21889351 doi:10.1016/j.str.2011.07.016
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