This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

5bnb

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

Crystal structure of a Ube2S-ubiquitin conjugate

Structural highlights

5bnb is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.49Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

UBE2S_HUMAN Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. Catalyzes 'Lys-11'-linked polyubiquitination. Acts as an essential factor of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated ubiquitin ligase that controls progression through mitosis. Acts by specifically elongating 'Lys-11'-linked polyubiquitin chains initiated by the E2 enzyme UBE2C/UBCH10 on APC/C substrates, enhancing the degradation of APC/C substrates by the proteasome and promoting mitotic exit. Also acts by elongating ubiquitin chains initiated by the E2 enzyme UBE2D1/UBCH5 in vitro; it is however unclear whether UBE2D1/UBCH5 acts as a E2 enzyme for the APC/C in vivo. Also involved in ubiquitination and subsequent degradation of VHL, resulting in an accumulation of HIF1A. In vitro able to promote polyubiquitination using all 7 ubiquitin Lys residues, except 'Lys-48'-linked polyubiquitination.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

Protein ubiquitination occurs through the sequential formation and reorganization of specific protein-protein interfaces. Ubiquitin-conjugating (E2) enzymes, such as Ube2S, catalyze the formation of an isopeptide linkage between the C-terminus of a "donor" ubiquitin and a primary amino group of an "acceptor" ubiquitin molecule. This reaction involves an intermediate, in which the C-terminus of the donor ubiquitin is thioester-bound to the active site cysteine of the E2 and a functionally important interface is formed between the two proteins. A docked model of a Ube2S-donor ubiquitin complex was generated previously, based on chemical shift mapping by NMR, and predicted contacts were validated in functional studies. We now present the crystal structure of a covalent Ube2S-ubiquitin complex. The structure contains an interface between Ube2S and ubiquitin in trans that resembles the earlier model in general terms, but differs in detail. The crystallographic interface is more hydrophobic than the earlier model and is stable in molecular dynamics (MD) simulations. Remarkably, the docked Ube2S-donor complex converges readily to the configuration seen in the crystal structure in 3 out of 8 MD trajectories. Since the crystallographic interface is fully consistent with mutational effects, this indicates that the structure provides an energetically favorable representation of the functionally critical Ube2S-donor interface.

Crystal Structure of a Ube2S-Ubiquitin Conjugate.,Lorenz S, Bhattacharyya M, Feiler C, Rape M, Kuriyan J PLoS One. 2016 Feb 1;11(2):e0147550. doi: 10.1371/journal.pone.0147550., eCollection 2016. PMID:26828794^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Jung CR, Hwang KS, Yoo J, Cho WK, Kim JM, Kim WH, Im DS. E2-EPF UCP targets pVHL for degradation and associates with tumor growth and metastasis. Nat Med. 2006 Jul;12(7):809-16. Epub 2006 Jul 2. PMID:16819549 doi:http://dx.doi.org/10.1038/nm1440
↑ Garnett MJ, Mansfeld J, Godwin C, Matsusaka T, Wu J, Russell P, Pines J, Venkitaraman AR. UBE2S elongates ubiquitin chains on APC/C substrates to promote mitotic exit. Nat Cell Biol. 2009 Nov;11(11):1363-9. doi: 10.1038/ncb1983. Epub 2009 Oct 11. PMID:19820702 doi:http://dx.doi.org/10.1038/ncb1983
↑ Williamson A, Wickliffe KE, Mellone BG, Song L, Karpen GH, Rape M. Identification of a physiological E2 module for the human anaphase-promoting complex. Proc Natl Acad Sci U S A. 2009 Oct 27;106(43):18213-8. doi:, 10.1073/pnas.0907887106. Epub 2009 Oct 12. PMID:19822757 doi:http://dx.doi.org/10.1073/pnas.0907887106
↑ David Y, Ziv T, Admon A, Navon A. The E2 ubiquitin conjugating enzymes direct polyubiquitination to preferred lysines. J Biol Chem. 2010 Jan 8. PMID:20061386 doi:M109.089003
↑ Bremm A, Freund SM, Komander D. Lys11-linked ubiquitin chains adopt compact conformations and are preferentially hydrolyzed by the deubiquitinase Cezanne. Nat Struct Mol Biol. 2010 Aug;17(8):939-47. Epub 2010 Jul 11. PMID:20622874 doi:10.1038/nsmb.1873
↑ Lorenz S, Bhattacharyya M, Feiler C, Rape M, Kuriyan J. Crystal Structure of a Ube2S-Ubiquitin Conjugate. PLoS One. 2016 Feb 1;11(2):e0147550. doi: 10.1371/journal.pone.0147550., eCollection 2016. PMID:26828794 doi:http://dx.doi.org/10.1371/journal.pone.0147550

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5bnb"

Categories: Homo sapiens | Large Structures | Feiler CG | Kuriyan J | Lorenz SG

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[5bnb]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BNB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BNB FirstGlance]. <br>
-</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=5bnb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bnb OCA], [https://pdbe.org/5bnb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bnb RCSB], [https://www.ebi.ac.uk/pdbsum/5bnb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bnb ProSAT]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.49&#8491;</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=5bnb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bnb OCA], [https://pdbe.org/5bnb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bnb RCSB], [https://www.ebi.ac.uk/pdbsum/5bnb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bnb ProSAT]</span></td></tr>
 </table>
 == Function ==

5bnb

From Proteopedia

Current revision

Crystal structure of a Ube2S-ubiquitin conjugate

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox