2oob

From Proteopedia

(Difference between revisions)

Revision as of 19:14, 25 December 2014

crystal structure of the UBA domain from Cbl-b ubiquitin ligase in complex with ubiquitin

Structural highlights

2oob is a 2 chain structure with sequence from Bos taurus and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	2oo9, 2ooa
Gene:	CBLB, RNF56 (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[CBLB_HUMAN] E3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome. Negatively regulates TCR (T-cell receptor), BCR (B-cell receptor) and FCER1 (high affinity immunoglobulin epsilon receptor) signal transduction pathways. In naive T-cells, inhibits VAV1 activation upon TCR engagement and imposes a requirement for CD28 costimulation for proliferation and IL-2 production. Also acts by promoting PIK3R1/p85 ubiquitination, which impairs its recruitment to the TCR and subsequent activation. In activated T-cells, inhibits PLCG1 activation and calcium mobilization upon restimulation and promotes anergy. In B-cells, acts by ubiquitinating SYK and promoting its proteasomal degradation. May also be involved in EGFR ubiquitination and internalization.^[1] ^[2] ^[3] ^[4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Cbl proteins are E3 ubiquitin ligases that are negative regulators of many receptor tyrosine kinases. Cbl-b and c-Cbl contain a ubiquitin-associated (UBA) domain, which is present in a variety of proteins involved in ubiquitin-mediated processes. Despite high sequence identity, Cbl UBA domains display remarkably different ubiquitin-binding properties. Here, we report the crystal structure of the UBA domain of Cbl-b in complex with ubiquitin at 1.9 A resolution. The structure reveals an atypical mechanism of ubiquitin recognition by the first helix of the UBA. Helices 2 and 3 of the UBA domain form a second binding surface, which mediates UBA dimerization in the crystal and in solution. Site-directed mutagenesis demonstrates that Cbl-b dimerization is regulated by ubiquitin binding and required for tyrosine phosphorylation of Cbl-b and ubiquitination of Cbl-b substrates. These studies demonstrate a role for ubiquitin in regulating biological activity by promoting protein dimerization.

Structural basis for ubiquitin-mediated dimerization and activation of the ubiquitin protein ligase Cbl-b.,Peschard P, Kozlov G, Lin T, Mirza IA, Berghuis AM, Lipkowitz S, Park M, Gehring K Mol Cell. 2007 Aug 3;27(3):474-85. PMID:17679095^[5]

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

References

↑ Elly C, Witte S, Zhang Z, Rosnet O, Lipkowitz S, Altman A, Liu YC. Tyrosine phosphorylation and complex formation of Cbl-b upon T cell receptor stimulation. Oncogene. 1999 Feb 4;18(5):1147-56. PMID:10022120 doi:10.1038/sj.onc.1202411
↑ Ettenberg SA, Keane MM, Nau MM, Frankel M, Wang LM, Pierce JH, Lipkowitz S. cbl-b inhibits epidermal growth factor receptor signaling. Oncogene. 1999 Mar 11;18(10):1855-66. PMID:10086340 doi:10.1038/sj.onc.1202499
↑ Fang D, Wang HY, Fang N, Altman Y, Elly C, Liu YC. Cbl-b, a RING-type E3 ubiquitin ligase, targets phosphatidylinositol 3-kinase for ubiquitination in T cells. J Biol Chem. 2001 Feb 16;276(7):4872-8. Epub 2000 Nov 21. PMID:11087752 doi:10.1074/jbc.M008901200
↑ Fang D, Liu YC. Proteolysis-independent regulation of PI3K by Cbl-b-mediated ubiquitination in T cells. Nat Immunol. 2001 Sep;2(9):870-5. PMID:11526404 doi:10.1038/ni0901-870
↑ Peschard P, Kozlov G, Lin T, Mirza IA, Berghuis AM, Lipkowitz S, Park M, Gehring K. Structural basis for ubiquitin-mediated dimerization and activation of the ubiquitin protein ligase Cbl-b. Mol Cell. 2007 Aug 3;27(3):474-85. PMID:17679095 doi:10.1016/j.molcel.2007.06.023

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2oob"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2oob]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OOB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2OOB FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2oo9|2oo9]], [[2ooa|2ooa]]</td></tr>
+</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2oo9|2oo9]], [[2ooa|2ooa]]</td></tr>
-<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CBLB, RNF56 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CBLB, RNF56 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2oob FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oob OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2oob RCSB], [http://www.ebi.ac.uk/pdbsum/2oob PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2oob FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oob OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2oob RCSB], [http://www.ebi.ac.uk/pdbsum/2oob PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/CBLB_HUMAN CBLB_HUMAN]] E3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome. Negatively regulates TCR (T-cell receptor), BCR (B-cell receptor) and FCER1 (high affinity immunoglobulin epsilon receptor) signal transduction pathways. In naive T-cells, inhibits VAV1 activation upon TCR engagement and imposes a requirement for CD28 costimulation for proliferation and IL-2 production. Also acts by promoting PIK3R1/p85 ubiquitination, which impairs its recruitment to the TCR and subsequent activation. In activated T-cells, inhibits PLCG1 activation and calcium mobilization upon restimulation and promotes anergy. In B-cells, acts by ubiquitinating SYK and promoting its proteasomal degradation. May also be involved in EGFR ubiquitination and internalization.<ref>PMID:10022120</ref> <ref>PMID:10086340</ref> <ref>PMID:11087752</ref> <ref>PMID:11526404</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 35: / Line 37: @@
 [[Category: Bos taurus]]
 [[Category: Homo sapiens]]
-[[Category: Gehring, K.]]
+[[Category: Gehring, K]]
-[[Category: Kozlov, G.]]
+[[Category: Kozlov, G]]
 [[Category: Ligase]]
 [[Category: Protein-protein complex]]

2oob

From Proteopedia

Revision as of 19:14, 25 December 2014

crystal structure of the UBA domain from Cbl-b ubiquitin ligase in complex with ubiquitin

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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