3buo

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
m (Protected "3buo" [edit=sysop:move=sysop])
Current revision (09:43, 6 November 2024) (edit) (undo)
 
(10 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:3buo.png|left|200px]]
 
-
<!--
+
==Crystal structure of c-Cbl-TKB domain complexed with its binding motif in EGF receptor'==
-
The line below this paragraph, containing "STRUCTURE_3buo", creates the "Structure Box" on the page.
+
<StructureSection load='3buo' size='340' side='right'caption='[[3buo]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
-
You may change the PDB parameter (which sets the PDB file loaded into the applet)
+
== Structural highlights ==
-
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+
<table><tr><td colspan='2'>[[3buo]] is a 4 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=3BUO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BUO FirstGlance]. <br>
-
or leave the SCENE parameter empty for the default display.
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
-
-->
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
-
{{STRUCTURE_3buo| PDB=3buo | SCENE= }}
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3buo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3buo OCA], [https://pdbe.org/3buo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3buo RCSB], [https://www.ebi.ac.uk/pdbsum/3buo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3buo ProSAT]</span></td></tr>
 +
</table>
 +
== Disease ==
 +
[https://www.uniprot.org/uniprot/EGFR_HUMAN EGFR_HUMAN] Defects in EGFR are associated with lung cancer (LNCR) [MIM:[https://omim.org/entry/211980 211980]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis.
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/EGFR_HUMAN EGFR_HUMAN] Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, amphiregulin, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade. Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin.<ref>PMID:7657591</ref> <ref>PMID:11602604</ref> <ref>PMID:12873986</ref> <ref>PMID:10805725</ref> <ref>PMID:11116146</ref> <ref>PMID:11483589</ref> <ref>PMID:17115032</ref> <ref>PMID:21258366</ref> <ref>PMID:12297050</ref> <ref>PMID:12620237</ref> <ref>PMID:15374980</ref> <ref>PMID:19560417</ref> <ref>PMID:20837704</ref> Isoform 2 may act as an antagonist of EGF action.<ref>PMID:7657591</ref> <ref>PMID:11602604</ref> <ref>PMID:12873986</ref> <ref>PMID:10805725</ref> <ref>PMID:11116146</ref> <ref>PMID:11483589</ref> <ref>PMID:17115032</ref> <ref>PMID:21258366</ref> <ref>PMID:12297050</ref> <ref>PMID:12620237</ref> <ref>PMID:15374980</ref> <ref>PMID:19560417</ref> <ref>PMID:20837704</ref>
 +
== Evolutionary Conservation ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bu/3buo_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3buo ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
The c-Cbl tyrosine kinase binding domain (Cbl-TKB), essentially an 'embedded' SH2 domain, has a critical role in targeting proteins for ubiquitination. To address how this domain can bind to disparate recognition mofits and to determine whether this results in variations in substrate-binding affinity, we compared crystal structures of the Cbl-TKB domain complexed with phosphorylated peptides of Sprouty2, Sprouty4, epidermal growth factor receptor, Syk, and c-Met receptors and validated the binding with point-mutational analyses using full-length proteins. An obligatory, intrapeptidyl H-bond between the phosphotyrosine and the conserved asparagine or adjacent arginine is essential for binding and orients the peptide into a positively charged pocket on c-Cbl. Surprisingly, c-Met bound to Cbl in the reverse direction, which is unprecedented for SH2 domain binding. The necessity of this intrapeptidyl H-bond was confirmed with isothermal titration calorimetry experiments that also showed Sprouty2 to have the highest binding affinity to c-Cbl; this may enable the selective sequestration of c-Cbl from other target proteins.
-
===Crystal structure of c-Cbl-TKB domain complexed with its binding motif in EGF receptor'===
+
Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates.,Ng C, Jackson RA, Buschdorf JP, Sun Q, Guy GR, Sivaraman J EMBO J. 2008 Mar 5;27(5):804-16. Epub 2008 Feb 14. PMID:18273061<ref>PMID:18273061</ref>
-
 
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
<!--
+
</div>
-
The line below this paragraph, {{ABSTRACT_PUBMED_18273061}}, adds the Publication Abstract to the page
+
<div class="pdbe-citations 3buo" style="background-color:#fffaf0;"></div>
-
(as it appears on PubMed at http://www.pubmed.gov), where 18273061 is the PubMed ID number.
+
-
-->
+
-
{{ABSTRACT_PUBMED_18273061}}
+
-
 
+
-
==About this Structure==
+
-
[[3buo]] is a 4 chain structure of [[Epidermal Growth Factor Receptor]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BUO OCA].
+
==See Also==
==See Also==
-
*[[Epidermal Growth Factor Receptor]]
+
*[[Epidermal growth factor receptor 3D structures|Epidermal growth factor receptor 3D structures]]
-
 
+
*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
-
==Reference==
+
== References ==
-
<ref group="xtra">PMID:18273061</ref><references group="xtra"/>
+
<references/>
 +
__TOC__
 +
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Buschdorf, J P.]]
+
[[Category: Large Structures]]
-
[[Category: Guy, G R.]]
+
[[Category: Buschdorf JP]]
-
[[Category: Jackson, R A.]]
+
[[Category: Guy GR]]
-
[[Category: Ng, C.]]
+
[[Category: Jackson RA]]
-
[[Category: Sivaraman, J.]]
+
[[Category: Ng C]]
-
[[Category: Sun, Q.]]
+
[[Category: Sivaraman J]]
-
[[Category: Alternative splicing]]
+
[[Category: Sun Q]]
-
[[Category: Anti-oncogene]]
+
-
[[Category: Atp-binding]]
+
-
[[Category: Calcium]]
+
-
[[Category: Cbl]]
+
-
[[Category: Cell cycle]]
+
-
[[Category: Complex]]
+
-
[[Category: Cytoplasm]]
+
-
[[Category: Disease mutation]]
+
-
[[Category: Glycoprotein]]
+
-
[[Category: Kinase]]
+
-
[[Category: Ligase]]
+
-
[[Category: Ligase/signaling protein complex]]
+
-
[[Category: Membrane]]
+
-
[[Category: Metal-binding]]
+
-
[[Category: Nucleotide-binding]]
+
-
[[Category: Phosphoprotein]]
+
-
[[Category: Polymorphism]]
+
-
[[Category: Proto-oncogene]]
+
-
[[Category: Receptor]]
+
-
[[Category: Secreted]]
+
-
[[Category: Sh2 domain]]
+
-
[[Category: Signal transduction]]
+
-
[[Category: Tkb]]
+
-
[[Category: Transferase]]
+
-
[[Category: Transmembrane]]
+
-
[[Category: Tyrosine-protein kinase]]
+
-
[[Category: Ubl conjugation]]
+
-
[[Category: Ubl conjugation pathway]]
+
-
[[Category: Zinc]]
+
-
[[Category: Zinc-finger]]
+

Current revision

Crystal structure of c-Cbl-TKB domain complexed with its binding motif in EGF receptor'

PDB ID 3buo

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3buo"
Personal tools