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| - | {{STRUCTURE_4jio| PDB=4jio | SCENE= }} | |
| - | ===Bro1 V domain and ubiquitin=== | |
| - | {{ABSTRACT_PUBMED_23726974}} | |
| | | | |
| - | ==Function== | + | ==Bro1 V domain and ubiquitin== |
| - | [[http://www.uniprot.org/uniprot/RL40_HUMAN RL40_HUMAN]] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.<ref>PMID:16543144</ref> <ref>PMID:19754430</ref> Ribosomal protein L40 is a component of the 60S subunit of the ribosome.<ref>PMID:16543144</ref> <ref>PMID:19754430</ref> | + | <StructureSection load='4jio' size='340' side='right'caption='[[4jio]], [[Resolution|resolution]] 3.60Å' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[4jio]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Naumovozyma_castellii Naumovozyma castellii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JIO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JIO FirstGlance]. <br> |
| | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.6Å</td></tr> |
| | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4jio FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jio OCA], [https://pdbe.org/4jio PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jio RCSB], [https://www.ebi.ac.uk/pdbsum/4jio PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jio ProSAT]</span></td></tr> |
| | + | </table> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | 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 cargos. 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-cargos. |
| | | | |
| - | ==About this Structure==
| + | The yeast alix homolog bro1 functions as a ubiquitin receptor for protein sorting into multivesicular endosomes.,Pashkova N, Gakhar L, Winistorfer SC, Sunshine AB, Rich M, Dunham MJ, Yu L, Piper RC Dev Cell. 2013 Jun 10;25(5):520-33. doi: 10.1016/j.devcel.2013.04.007. Epub 2013 , May 30. PMID:23726974<ref>PMID:23726974</ref> |
| - | [[4jio]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Naumovozyma_castellii_cbs_4309 Naumovozyma castellii cbs 4309]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JIO OCA].
| + | |
| | | | |
| - | ==Reference==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | <ref group="xtra">PMID:023726974</ref><references group="xtra"/><references/> | + | </div> |
| | + | <div class="pdbe-citations 4jio" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[3D structures of ubiquitin|3D structures of ubiquitin]] |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Naumovozyma castellii cbs 4309]] | + | [[Category: Large Structures]] |
| - | [[Category: Gakhar, L.]] | + | [[Category: Naumovozyma castellii]] |
| - | [[Category: Pashkova, N.]] | + | [[Category: Gakhar L]] |
| - | [[Category: Piper, R C.]] | + | [[Category: Pashkova N]] |
| - | [[Category: Endosome]]
| + | [[Category: Piper RC]] |
| - | [[Category: Escrt-i]]
| + | |
| - | [[Category: Escrt-iii]]
| + | |
| - | [[Category: Membrane trafficking]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Ubiquitin]]
| + | |
| Structural highlights
Publication Abstract from PubMed
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 cargos. 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-cargos.
The yeast alix homolog bro1 functions as a ubiquitin receptor for protein sorting into multivesicular endosomes.,Pashkova N, Gakhar L, Winistorfer SC, Sunshine AB, Rich M, Dunham MJ, Yu L, Piper RC Dev Cell. 2013 Jun 10;25(5):520-33. doi: 10.1016/j.devcel.2013.04.007. Epub 2013 , May 30. PMID:23726974[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Pashkova N, Gakhar L, Winistorfer SC, Sunshine AB, Rich M, Dunham MJ, Yu L, Piper RC. The yeast alix homolog bro1 functions as a ubiquitin receptor for protein sorting into multivesicular endosomes. Dev Cell. 2013 Jun 10;25(5):520-33. doi: 10.1016/j.devcel.2013.04.007. Epub 2013 , May 30. PMID:23726974 doi:10.1016/j.devcel.2013.04.007
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