5af6 | pdb_00005af6

Structure of Lys33-linked diUb bound to Trabid NZF1

Structural highlights

5af6 is a 10 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	ZN
Related:	5af4, 5af5
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ZRAN1_HUMAN] Specifically hydrolyzes 'Lys-29'-linked and 'Lys-33'-linked diubiquitin. Also cleaves 'Lys-63'-linked chains, but with 40-fold less efficiency compared to 'Lys-29'-linked ones. Positive regulator of the Wnt signaling pathway that deubiquitinates APC protein, a negative regulator of Wnt-mediated transcription. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the stress fiber dynamics and cell migration. May also modulate TNF-alpha signaling.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Protein ubiquitination regulates many cellular processes via attachment of structurally and functionally distinct ubiquitin (Ub) chains. Several atypical chain types have remained poorly characterized because the enzymes mediating their assembly and receptors with specific binding properties have been elusive. We found that the human HECT E3 ligases UBE3C and AREL1 assemble K48/K29- and K11/K33-linked Ub chains, respectively, and can be used in combination with DUBs to generate K29- and K33-linked chains for biochemical and structural analyses. Solution studies indicate that both chains adopt open and dynamic conformations. We further show that the N-terminal Npl4-like zinc finger (NZF1) domain of the K29/K33-specific deubiquitinase TRABID specifically binds K29/K33-linked diUb, and a crystal structure of this complex explains TRABID specificity and suggests a model for chain binding by TRABID. Our work uncovers linkage-specific components in the Ub system for atypical K29- and K33-linked Ub chains, providing tools to further understand these unstudied posttranslational modifications.

Assembly and Specific Recognition of K29- and K33-Linked Polyubiquitin.,Michel MA, Elliott PR, Swatek KN, Simicek M, Pruneda JN, Wagstaff JL, Freund SM, Komander D Mol Cell. 2015 Mar 4. pii: S1097-2765(15)00091-X. doi:, 10.1016/j.molcel.2015.01.042. PMID:25752577^[5]

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

References

↑ Tran H, Hamada F, Schwarz-Romond T, Bienz M. Trabid, a new positive regulator of Wnt-induced transcription with preference for binding and cleaving K63-linked ubiquitin chains. Genes Dev. 2008 Feb 15;22(4):528-42. doi: 10.1101/gad.463208. PMID:18281465 doi:https://dx.doi.org/10.1101/gad.463208
↑ Bai SW, Herrera-Abreu MT, Rohn JL, Racine V, Tajadura V, Suryavanshi N, Bechtel S, Wiemann S, Baum B, Ridley AJ. Identification and characterization of a set of conserved and new regulators of cytoskeletal organization, cell morphology and migration. BMC Biol. 2011 Aug 11;9:54. doi: 10.1186/1741-7007-9-54. PMID:21834987 doi:10.1186/1741-7007-9-54
↑ Mevissen TE, Hospenthal MK, Geurink PP, Elliott PR, Akutsu M, Arnaudo N, Ekkebus R, Kulathu Y, Wauer T, El Oualid F, Freund SM, Ovaa H, Komander D. OTU Deubiquitinases Reveal Mechanisms of Linkage Specificity and Enable Ubiquitin Chain Restriction Analysis. Cell. 2013 Jul 3;154(1):169-84. doi: 10.1016/j.cell.2013.05.046. PMID:23827681 doi:10.1016/j.cell.2013.05.046
↑ Licchesi JD, Mieszczanek J, Mevissen TE, Rutherford TJ, Akutsu M, Virdee S, Oualid FE, Chin JW, Ovaa H, Bienz M, Komander D. An ankyrin-repeat ubiquitin-binding domain determines TRABID's specificity for atypical ubiquitin chains. Nat Struct Mol Biol. 2011 Dec 11;19(1):62-71. doi: 10.1038/nsmb.2169. PMID:22157957 doi:10.1038/nsmb.2169
↑ Michel MA, Elliott PR, Swatek KN, Simicek M, Pruneda JN, Wagstaff JL, Freund SM, Komander D. Assembly and Specific Recognition of K29- and K33-Linked Polyubiquitin. Mol Cell. 2015 Mar 4. pii: S1097-2765(15)00091-X. doi:, 10.1016/j.molcel.2015.01.042. PMID:25752577 doi:https://dx.doi.org/10.1016/j.molcel.2015.01.042

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OCA

[1] Tran H, Hamada F, Schwarz-Romond T, Bienz M. Trabid, a new positive regulator of Wnt-induced transcription with preference for binding and cleaving K63-linked ubiquitin chains. Genes Dev. 2008 Feb 15;22(4):528-42. doi: 10.1101/gad.463208. PMID:18281465 doi:https://dx.doi.org/10.1101/gad.463208

[2] Bai SW, Herrera-Abreu MT, Rohn JL, Racine V, Tajadura V, Suryavanshi N, Bechtel S, Wiemann S, Baum B, Ridley AJ. Identification and characterization of a set of conserved and new regulators of cytoskeletal organization, cell morphology and migration. BMC Biol. 2011 Aug 11;9:54. doi: 10.1186/1741-7007-9-54. PMID:21834987 doi:10.1186/1741-7007-9-54

[3] Mevissen TE, Hospenthal MK, Geurink PP, Elliott PR, Akutsu M, Arnaudo N, Ekkebus R, Kulathu Y, Wauer T, El Oualid F, Freund SM, Ovaa H, Komander D. OTU Deubiquitinases Reveal Mechanisms of Linkage Specificity and Enable Ubiquitin Chain Restriction Analysis. Cell. 2013 Jul 3;154(1):169-84. doi: 10.1016/j.cell.2013.05.046. PMID:23827681 doi:10.1016/j.cell.2013.05.046

[4] Licchesi JD, Mieszczanek J, Mevissen TE, Rutherford TJ, Akutsu M, Virdee S, Oualid FE, Chin JW, Ovaa H, Bienz M, Komander D. An ankyrin-repeat ubiquitin-binding domain determines TRABID's specificity for atypical ubiquitin chains. Nat Struct Mol Biol. 2011 Dec 11;19(1):62-71. doi: 10.1038/nsmb.2169. PMID:22157957 doi:10.1038/nsmb.2169

[5] Michel MA, Elliott PR, Swatek KN, Simicek M, Pruneda JN, Wagstaff JL, Freund SM, Komander D. Assembly and Specific Recognition of K29- and K33-Linked Polyubiquitin. Mol Cell. 2015 Mar 4. pii: S1097-2765(15)00091-X. doi:, 10.1016/j.molcel.2015.01.042. PMID:25752577 doi:https://dx.doi.org/10.1016/j.molcel.2015.01.042

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5af6 | pdb_00005af6

Structure of Lys33-linked diUb bound to Trabid NZF1

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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