4JJY

Alix V domain

Summary for 4JJY

• Entry DOI: 10.2210/pdb4jjy/pdb
• Descriptor: Programmed cell death 6-interacting protein (1 entity in total)
• Functional Keywords: ubiquitin, endosome, membrane trafficking, virus budding, escrti, protein binding
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytosol: Q8WUM4
• Total number of polymer chains: 2
• Total formula weight: 81796.75

Authors

Pashkova, N.,Gakhar, L.,Yu, L.,Piper, R.C. (deposition date: 2013-03-08, release date: 2013-06-19, Last modification date: 2024-11-20)

Primary citation

Pashkova, N.,Gakhar, L.,Winistorfer, S.C.,Sunshine, A.B.,Rich, M.,Dunham, M.J.,Yu, L.,Piper, R.C.
The yeast alix homolog bro1 functions as a ubiquitin receptor for protein sorting into multivesicular endosomes.
Dev.Cell, 25:520-533, 2013

PubMed Abstract: Sorting of ubiquitinated membrane proteins into lumenal vesicles of multivesicular bodies is mediated by the Endosomal Sorting Complex Required for Transport (ESCRT) apparatus and accessory proteins such as Bro1, which recruits the deubiquitinating enzyme Doa4 to remove ubiquitin from cargo. Here we propose that Bro1 works as a receptor for the selective sorting of ubiquitinated cargoes. We found synthetic genetic interactions between BRO1 and ESCRT-0, suggesting that Bro1 functions similarly to ESCRT-0. Multiple structural approaches demonstrated that Bro1 binds ubiquitin via the N-terminal trihelical arm of its middle V domain. Mutants of Bro1 that lack the ability to bind Ub were dramatically impaired in their ability to sort Ub-cargo membrane proteins, but only when combined with hypomorphic alleles of ESCRT-0. These data suggest that Bro1 and other Bro1 family members function in parallel with ESCRT-0 to recognize and sort Ub-cargoes.

PubMed: 23726974
DOI: 10.1016/j.devcel.2013.04.007

Experimental method

X-RAY DIFFRACTION (6.503 Å)