|PROSITE documentation PDOC51495|
The multivesicular body (MVB) protein-sorting pathway targets transmembrane proteins either for degradation or for function in the vacuole/lysosomes. The signal for entry into this pathway is monoubiquitination of protein cargo, which results in incorporation of cargo into luminal vesicles at late endosomes. Another crucial player is phosphatidylinositol 3-phosphate (PtdINS(3)P), which is enriched on early endosomes and on the luminal vesicles of MVBs. The ESCRT complexes are critical for MVB budding and sorting of monoubiquitinated cargo into the luminal vesicles. Various Ub-binding domains (UBDs), such as UIM (see <PDOC50330>), UEV and NZF are found in such machineries. The Vps 36 subunit of the ESCRT-II trafficking complex binds both phosphoinositides and ubiquitin. All members of the Vps36 family contain a divergent GRAM/PH-like domain and yeast and some other fungi have one or two NZF domains inserted in the GRAM/PH-like domain. This N-terminal region of Vps36 (EAP45) has been named the GLUE (GRAM-like ubiquitin-binding in EAP45) domain. The GLUE domain acts as a central cog driving the endosomal ESCRT machinery, through simultaneous interactions with PtdIns3P-containing membranes, ubiquitin, and ESCRT-I. Like other known ubiquitin-binding domains, the GLUE domain interacts with the hydrophobic surface patch of ubiquitin. The GLUE domain is the first ubiquitin-binding domain shown to bind phosphoinositides, and the ability of the same domain to bind both ubiquitin and a phosphoinositide opens interesting possibilities for coordination of membrane interactions and cargo recognition [1,2,3,4,5].
The GLUE domain has a split PH-domain fold with two curved β sheets and one long α helix (see <PDB:2CAY>). The two sheets (β1-β4 and β5-β7) form a β barrel-like structure,The C-terminal α helix is wedged between the two β sheets, covering a hydrophobic core. The Vps36 GLUE domain binds PtdIns3P via a positively charged lipid binding pocket, delineated by the variable loops β1/β2, β5/β6 and β7/α1, in contrast to the vast majority of characterized PH domains, which use a different lipid binding pocket [2,3].
The profile we developed covers the entire GLUE domain.Last update:
July 2011 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Slagsvold T. Aasland R. Hirano S. Bache K.G. Raiborg C. Trambaiolo D. Wakatsuki S. Stenmark H.|
|Title||Eap45 in mammalian ESCRT-II binds ubiquitin via a phosphoinositide-interacting GLUE domain.|
|Source||J. Biol. Chem. 280:19600-19606(2005).|
|2||Authors||Teo H. Gill D.J. Sun J. Perisic O. Veprintsev D.B. Vallis Y. Emr S.D. Williams R.L.|
|Title||ESCRT-I core and ESCRT-II GLUE domain structures reveal role for GLUE in linking to ESCRT-I and membranes.|
|3||Authors||Hirano S. Suzuki N. Slagsvold T. Kawasaki M. Trambaiolo D. Kato R. Stenmark H. Wakatsuki S.|
|Title||Structural basis of ubiquitin recognition by mammalian Eap45 GLUE domain.|
|Source||Nat. Struct. Mol. Biol. 13:1031-1032(2006).|
|4||Authors||Eathiraj S. Lambright D.G.|
|Title||ESCRT complexes assembled and GLUEd.|
|5||Authors||Hurley J.H. Lee S. Prag G.|
|Source||Biochem. J. 399:361-372(2006).|