Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
XB-ART-39302
Biochem J March 1, 2009; 418 (2): 277-84.
Show Gene links Show Anatomy links

The CHMP4b- and Src-docking sites in the Bro1 domain are autoinhibited in the native state of Alix.

Zhou X , Pan S , Sun L , Corvera J , Lee YC , Lin SH , Kuang J .


Abstract
The Bro1 domain of Alix [ALG-2 (apoptosis-linked gene 2)-interacting protein X], which plays important roles in endosomal sorting and multiple ESCRT (endosomal sorting complex required for transport)-linked processes, contains the docking sites for the ESCRT-III component CHMP4b (charged multivesicular body protein 4b) and the regulatory tyrosine kinase, Src. Although the structural bases for these docking sites have been defined by crystallography studies, it has not been determined whether these sites are available in the native state of Alix. In the present study, we demonstrate that these two docking sites are unavailable in recombinant Alix under native conditions and that their availabilities can be induced by detergents. In HEK (human embryonic kidney)-293 cell lysates, these two docking sites are not available in cytosolic Alix, but are available in membrane-bound Alix. These findings show that the native state of Alix does not have a functional Bro1 domain and predict that Alix''s involvement in endosomal sorting and other ESCRT-linked processes requires an activation step that relieves the autoinhibition of the Bro1 domain.

PubMed ID: 19016654
Article link: Biochem J
Grant support: [+]

Species referenced: Xenopus
Genes referenced: cep55 chmp4b pdcd6ip