| Structural highlights
Function
[VPS27_YEAST] Component of the ESCRT-0 complex which is the sorting receptor for ubiquitinated cargo proteins at the multivesicular body (MVB) and recruits ESCRT-I to the MVB outer membrane. Controls exit from the prevacuolar compartment (PVC) in both the forward direction to the vacuole and the return to the Golgi. Allows VPS10 to return to the (trans-Golgi network) TGN from the PVC. Might also function as an alternate adapter in the COPIb clathrin-like coat.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16]
Publication Abstract from PubMed
Ubiquitylation is used to target proteins into a large number of different biological processes including proteasomal degradation, endocytosis, virus budding, and vacuolar protein sorting (Vps). Ubiquitylated proteins are typically recognized using one of several different conserved ubiquitin binding modules. Here, we report the crystal structure and ubiquitin binding properties of one such module, the ubiquitin-interacting motif (UIM). We found that UIM peptides from several proteins involved in endocytosis and vacuolar protein sorting including Hrs, Vps27p, Stam1, and Eps15 bound specifically, but with modest affinity (Kd = 0.1-1 mm), to free ubiquitin. Full affinity ubiquitin binding required the presence of conserved acidic patches at the N and C terminus of the UIM, as well as highly conserved central alanine and serine residues. NMR chemical shift perturbation mapping experiments demonstrated that all of these UIM peptides bind to the I44 surface of ubiquitin. The 1.45 A resolution crystal structure of the second yeast Vps27p UIM (Vps27p-2) revealed that the ubiquitin-interacting motif forms an amphipathic helix. Although Vps27p-2 is monomeric in solution, the motif unexpectedly crystallized as an antiparallel four-helix bundle, and the potential biological implications of UIM oligomerization are therefore discussed.
Structure and ubiquitin binding of the ubiquitin-interacting motif.,Fisher RD, Wang B, Alam SL, Higginson DS, Robinson H, Sundquist WI, Hill CP J Biol Chem. 2003 Aug 1;278(31):28976-84. Epub 2003 May 14. PMID:12750381[17]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
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- ↑ Dupre S, Haguenauer-Tsapis R. Deubiquitination step in the endocytic pathway of yeast plasma membrane proteins: crucial role of Doa4p ubiquitin isopeptidase. Mol Cell Biol. 2001 Jul;21(14):4482-94. PMID:11416128 doi:10.1128/MCB.21.14.4482-4494.2001
- ↑ Bilodeau PS, Urbanowski JL, Winistorfer SC, Piper RC. The Vps27p Hse1p complex binds ubiquitin and mediates endosomal protein sorting. Nat Cell Biol. 2002 Jul;4(7):534-9. PMID:12055639 doi:10.1038/ncb815
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- ↑ Katzmann DJ, Stefan CJ, Babst M, Emr SD. Vps27 recruits ESCRT machinery to endosomes during MVB sorting. J Cell Biol. 2003 Aug 4;162(3):413-23. PMID:12900393 doi:http://dx.doi.org/10.1083/jcb.200302136
- ↑ Bilodeau PS, Winistorfer SC, Kearney WR, Robertson AD, Piper RC. Vps27-Hse1 and ESCRT-I complexes cooperate to increase efficiency of sorting ubiquitinated proteins at the endosome. J Cell Biol. 2003 Oct 27;163(2):237-43. PMID:14581452 doi:10.1083/jcb.200305007
- ↑ Eguez L, Chung YS, Kuchibhatla A, Paidhungat M, Garrett S. Yeast Mn2+ transporter, Smf1p, is regulated by ubiquitin-dependent vacuolar protein sorting. Genetics. 2004 May;167(1):107-17. PMID:15166140
- ↑ Eugster A, Pecheur EI, Michel F, Winsor B, Letourneur F, Friant S. Ent5p is required with Ent3p and Vps27p for ubiquitin-dependent protein sorting into the multivesicular body. Mol Biol Cell. 2004 Jul;15(7):3031-41. Epub 2004 Apr 23. PMID:15107463 doi:10.1091/mbc.E03-11-0793
- ↑ Bowers K, Lottridge J, Helliwell SB, Goldthwaite LM, Luzio JP, Stevens TH. Protein-protein interactions of ESCRT complexes in the yeast Saccharomyces cerevisiae. Traffic. 2004 Mar;5(3):194-210. PMID:15086794 doi:10.1111/j.1600-0854.2004.00169.x
- ↑ Gabriely G, Kama R, Gerst JE. Involvement of specific COPI subunits in protein sorting from the late endosome to the vacuole in yeast. Mol Cell Biol. 2007 Jan;27(2):526-40. Epub 2006 Nov 13. PMID:17101773 doi:MCB.00577-06
- ↑ Curtiss M, Jones C, Babst M. Efficient cargo sorting by ESCRT-I and the subsequent release of ESCRT-I from multivesicular bodies requires the subunit Mvb12. Mol Biol Cell. 2007 Feb;18(2):636-45. Epub 2006 Nov 29. PMID:17135292 doi:E06-07-0588
- ↑ Fisher RD, Wang B, Alam SL, Higginson DS, Robinson H, Sundquist WI, Hill CP. Structure and ubiquitin binding of the ubiquitin-interacting motif. J Biol Chem. 2003 Aug 1;278(31):28976-84. Epub 2003 May 14. PMID:12750381 doi:10.1074/jbc.M302596200
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