Structural highlights
Function
[BRO1_YEAST] Class E VPS protein involved in concentration and sorting of cargo proteins of the multivesicular body (MVB) for incorporation into intralumenal vesicles. Fusion between endosomes and the vacuole will then target the cargo proteins to the vacuolar lumen. Acts as an adapter that recruits the DOA4 deubiquitinase to the endosomes, leading to deubiquitination of cargo proteins prior to the lumenal sequestration. Its association to the endosomes depends on SNF7 and its dissociation requires VPS4. Interacts functionally with the Pkc1p-mitogen-activated protein kinase pathway.[1] [2] [3] [4] [5] [6]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Proteins delivered to the lysosome or the yeast vacuole via late endosomes are sorted by the ESCRT complexes and by associated proteins, including Alix and its yeast homolog Bro1. Alix, Bro1, and several other late endosomal proteins share a conserved 160 residue Bro1 domain whose boundaries, structure, and function have not been characterized. The crystal structure of the Bro1 domain of Bro1 reveals a folded core of 367 residues. The extended Bro1 domain is necessary and sufficient for binding to the ESCRT-III subunit Snf7 and for the recruitment of Bro1 to late endosomes. The structure resembles a boomerang with its concave face filled in and contains a triple tetratricopeptide repeat domain as a substructure. Snf7 binds to a conserved hydrophobic patch on Bro1 that is required for protein complex formation and for the protein-sorting function of Bro1. These results define a conserved mechanism whereby Bro1 domain-containing proteins are targeted to endosomes by Snf7 and its orthologs.
Structural basis for endosomal targeting by the Bro1 domain.,Kim J, Sitaraman S, Hierro A, Beach BM, Odorizzi G, Hurley JH Dev Cell. 2005 Jun;8(6):937-47. PMID:15935782[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Nickas ME, Yaffe MP. BRO1, a novel gene that interacts with components of the Pkc1p-mitogen-activated protein kinase pathway in Saccharomyces cerevisiae. Mol Cell Biol. 1996 Jun;16(6):2585-93. PMID:8649366
- ↑ Forsberg H, Hammar M, Andreasson C, Moliner A, Ljungdahl PO. Suppressors of ssy1 and ptr3 null mutations define novel amino acid sensor-independent genes in Saccharomyces cerevisiae. Genetics. 2001 Jul;158(3):973-88. PMID:11454748
- ↑ Springael JY, Nikko E, Andre B, Marini AM. Yeast Npi3/Bro1 is involved in ubiquitin-dependent control of permease trafficking. FEBS Lett. 2002 Apr 24;517(1-3):103-9. PMID:12062418
- ↑ Odorizzi G, Katzmann DJ, Babst M, Audhya A, Emr SD. Bro1 is an endosome-associated protein that functions in the MVB pathway in Saccharomyces cerevisiae. J Cell Sci. 2003 May 15;116(Pt 10):1893-903. Epub 2003 Mar 18. PMID:12668726 doi:http://dx.doi.org/10.1242/jcs.00395
- ↑ Nikko E, Marini AM, Andre B. Permease recycling and ubiquitination status reveal a particular role for Bro1 in the multivesicular body pathway. J Biol Chem. 2003 Dec 12;278(50):50732-43. Epub 2003 Sep 30. PMID:14523026 doi:http://dx.doi.org/10.1074/jbc.M306953200
- ↑ Luhtala N, Odorizzi G. Bro1 coordinates deubiquitination in the multivesicular body pathway by recruiting Doa4 to endosomes. J Cell Biol. 2004 Aug 30;166(5):717-29. Epub 2004 Aug 23. PMID:15326198 doi:http://dx.doi.org/10.1083/jcb.200403139
- ↑ Kim J, Sitaraman S, Hierro A, Beach BM, Odorizzi G, Hurley JH. Structural basis for endosomal targeting by the Bro1 domain. Dev Cell. 2005 Jun;8(6):937-47. PMID:15935782 doi:10.1016/j.devcel.2005.04.001
