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5tdb

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Revision as of 08:17, 8 January 2020

Crystal structure of the human UBR-box domain from UBR2 in complex with asymmetrically double methylated arginine peptide

Structural highlights

5tdb is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Related:	5tda, 5tdc, 5tdd
Gene:	UBR2, C6orf133, KIAA0349 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[UBR2_HUMAN] E3 ubiquitin-protein ligase which is a component of the N-end rule pathway. Recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation. Plays a critical role in chromatin inactivation and chromosome-wide transcriptional silencing during meiosis via ubiquitination of histone H2A. Binds leucine and is a negative regulator of the leucine-mTOR signaling pathway, thereby controlling cell growth.^[1] ^[2] ^[3]

Publication Abstract from PubMed

The N-end rule pathway controls the half-life of proteins based on their N-terminal residue. Positively charged type 1 N-degrons are recognized by a negatively charged pocket on the Zn finger named the UBR box. Here, we show that the UBR box is rigid, but bound water molecules in the pocket provide the structural plasticity required to bind different positively charged amino acids. Ultra-high-resolution crystal structures of arginine, histidine, and methylated arginine reveal that water molecules mediate the binding of N-degron peptides. Using a high-throughput binding assay and isothermal titration calorimetry, we demonstrate that the UBR box is able to bind methylated arginine and lysine peptides with high affinity and measure the preference for hydrophobic residues in the second position in the N-degron peptide. Finally, we show that the V122L mutation present in Johanson-Blizzard syndrome patients changes the specificity for the second position due to occlusion of the secondary pocket.

Bound Waters Mediate Binding of Diverse Substrates to a Ubiquitin Ligase.,Munoz-Escobar J, Matta-Camacho E, Cho C, Kozlov G, Gehring K Structure. 2017 Mar 27. pii: S0969-2126(17)30064-3. doi:, 10.1016/j.str.2017.03.004. PMID:28392261^[4]

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

References

↑ Kwak KS, Zhou X, Solomon V, Baracos VE, Davis J, Bannon AW, Boyle WJ, Lacey DL, Han HQ. Regulation of protein catabolism by muscle-specific and cytokine-inducible ubiquitin ligase E3alpha-II during cancer cachexia. Cancer Res. 2004 Nov 15;64(22):8193-8. PMID:15548684 doi:http://dx.doi.org/64/22/8193
↑ Kume K, Iizumi Y, Shimada M, Ito Y, Kishi T, Yamaguchi Y, Handa H. Role of N-end rule ubiquitin ligases UBR1 and UBR2 in regulating the leucine-mTOR signaling pathway. Genes Cells. 2010 Apr 1;15(4):339-49. doi: 10.1111/j.1365-2443.2010.01385.x. Epub, 2010 Mar 16. PMID:20298436 doi:http://dx.doi.org/10.1111/j.1365-2443.2010.01385.x
↑ Matta-Camacho E, Kozlov G, Li FF, Gehring K. Structural basis of substrate recognition and specificity in the N-end rule pathway. Nat Struct Mol Biol. 2010 Oct;17(10):1182-7. Epub 2010 Sep 12. PMID:20835242 doi:10.1038/nsmb.1894
↑ Munoz-Escobar J, Matta-Camacho E, Cho C, Kozlov G, Gehring K. Bound Waters Mediate Binding of Diverse Substrates to a Ubiquitin Ligase. Structure. 2017 Mar 27. pii: S0969-2126(17)30064-3. doi:, 10.1016/j.str.2017.03.004. PMID:28392261 doi:http://dx.doi.org/10.1016/j.str.2017.03.004

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/5tdb"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the human UBR-box domain from UBR2 in complex with asymmetrically double methylated arginine peptide==
-<StructureSection load='5tdb' size='340' side='right' caption='[[5tdb]], [[Resolution|resolution]] 1.10&Aring;' scene=''>
+<StructureSection load='5tdb' size='340' side='right'caption='[[5tdb]], [[Resolution|resolution]] 1.10&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[5tdb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TDB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TDB FirstGlance]. <br>
@@ Line 21: / Line 21: @@
 </div>
 <div class="pdbe-citations 5tdb" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Ubiquitin protein ligase|Ubiquitin protein ligase]]
 == References ==
 <references/>
@@ Line 26: / Line 29: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Gehring, K]]
 [[Category: Kozlov, G]]

5tdb

From Proteopedia

Revision as of 08:17, 8 January 2020

Crystal structure of the human UBR-box domain from UBR2 in complex with asymmetrically double methylated arginine peptide

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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