View source for 3zni


==Structure of phosphoTyr363-Cbl-b - UbcH5B-Ub - ZAP-70 peptide complex==
<StructureSection load='3zni' size='340' side='right'caption='[[3zni]], [[Resolution|resolution]] 2.21&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3zni]] is a 16 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=3ZNI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZNI 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]] 2.21&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=3zni FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zni OCA], [https://pdbe.org/3zni PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zni RCSB], [https://www.ebi.ac.uk/pdbsum/3zni PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zni ProSAT]</span></td></tr>
</table>
== Function ==
[https://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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
RING E3 ligases catalyze the transfer of ubiquitin (Ub) from E2 ubiquitin-conjugating enzyme thioesterified with Ub (E2~Ub) to substrate. For RING E3 dimers, the RING domain of one subunit and tail of the second cooperate to prime Ub, but how this is accomplished by monomeric RING E3s in the absence of a tail-like component is currently unknown. Here, we present a crystal structure of a monomeric RING E3, Tyr363-phosphorylated human CBL-B, bound to a stabilized Ub-linked E2, revealing a similar mechanism in activating E2~Ub. Both pTyr363 and the pTyr363-induced element interact directly with Ub's Ile36 surface, improving the catalytic efficiency of Ub transfer by ~200-fold. Hence, interactions outside the canonical RING domain are crucial for optimizing Ub transfer in both monomeric and dimeric RING E3s. We propose that an additional non-RING Ub-priming element may be a common RING E3 feature.

Essentiality of a non-RING element in priming donor ubiquitin for catalysis by a monomeric E3.,Dou H, Buetow L, Sibbet GJ, Cameron K, Huang DT Nat Struct Mol Biol. 2013 Jul 14. doi: 10.1038/nsmb.2621. PMID:23851457<ref>PMID:23851457</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3zni" style="background-color:#fffaf0;"></div>

==See Also==
*[[3D structures of ubiquitin|3D structures of ubiquitin]]
*[[3D structures of ubiquitin conjugating enzyme|3D structures of ubiquitin conjugating enzyme]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Buetow L]]
[[Category: Cameron K]]
[[Category: Dou H]]
[[Category: Huang DT]]
[[Category: Sibbet GJ]]