3g5v

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
m (Protected "3g5v" [edit=sysop:move=sysop])
Current revision (05:50, 17 October 2024) (edit) (undo)
 
(7 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:3g5v.png|left|200px]]
 
-
<!--
+
==Antibodies Specifically Targeting a Locally Misfolded Region of Tumor Associated EGFR==
-
The line below this paragraph, containing "STRUCTURE_3g5v", creates the "Structure Box" on the page.
+
<StructureSection load='3g5v' size='340' side='right'caption='[[3g5v]], [[Resolution|resolution]] 2.00&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'>[[3g5v]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3G5V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3G5V 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]] 2.001&#8491;</td></tr>
-
-->
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
-
{{STRUCTURE_3g5v| PDB=3g5v | SCENE= }}
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3g5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3g5v OCA], [https://pdbe.org/3g5v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3g5v RCSB], [https://www.ebi.ac.uk/pdbsum/3g5v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3g5v 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/g5/3g5v_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=3g5v ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Epidermal Growth Factor Receptor (EGFR) is involved in stimulating the growth of many human tumors, but the success of therapeutic agents has been limited in part by interference from the EGFR on normal tissues. Previously, we reported an antibody (mab806) against a truncated form of EGFR found commonly in gliomas. Remarkably, it also recognizes full-length EGFR on tumor cells but not on normal cells. However, the mechanism for this activity was unclear. Crystallographic structures for Fab:EGFR(287-302) complexes of mAb806 (and a second, related antibody, mAb175) show that this peptide epitope adopts conformations similar to those found in the wtEGFR. However, in both conformations observed for wtEGFR, tethered and untethered, antibody binding would be prohibited by significant steric clashes with the CR1 domain. Thus, these antibodies must recognize a cryptic epitope in EGFR. Structurally, it appeared that breaking the disulfide bond preceding the epitope might allow the CR1 domain to open up sufficiently for antibody binding. The EGFR(C271A/C283A) mutant not only binds mAb806, but binds with 1:1 stoichiometry, which is significantly greater than wtEGFR binding. Although mAb806 and mAb175 decrease tumor growth in xenografts displaying mutant, overexpressed, or autocrine stimulated EGFR, neither antibody inhibits the in vitro growth of cells expressing wtEGFR. In contrast, mAb806 completely inhibits the ligand-associated stimulation of cells expressing EGFR(C271A/C283A). Clearly, the binding of mAb806 and mAb175 to the wtEGFR requires the epitope to be exposed either during receptor activation, mutation, or overexpression. This mechanism suggests the possibility of generating antibodies to target other wild-type receptors on tumor cells.
-
===Antibodies Specifically Targeting a Locally Misfolded Region of Tumor Associated EGFR===
+
Antibodies specifically targeting a locally misfolded region of tumor associated EGFR.,Garrett TP, Burgess AW, Gan HK, Luwor RB, Cartwright G, Walker F, Orchard SG, Clayton AH, Nice EC, Rothacker J, Catimel B, Cavenee WK, Old LJ, Stockert E, Ritter G, Adams TE, Hoyne PA, Wittrup D, Chao G, Cochran JR, Luo C, Lou M, Huyton T, Xu Y, Fairlie WD, Yao S, Scott AM, Johns TG Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5082-7. Epub 2009 Mar 16. PMID:19289842<ref>PMID:19289842</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_19289842}}, adds the Publication Abstract to the page
+
<div class="pdbe-citations 3g5v" style="background-color:#fffaf0;"></div>
-
(as it appears on PubMed at http://www.pubmed.gov), where 19289842 is the PubMed ID number.
+
-
-->
+
-
{{ABSTRACT_PUBMED_19289842}}
+
-
 
+
-
==About this Structure==
+
-
[[3g5v]] is a 3 chain structure of [[Epidermal Growth Factor Receptor]] with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3G5V OCA].
+
==See Also==
==See Also==
-
*[[Epidermal Growth Factor Receptor]]
+
*[[Epidermal growth factor receptor 3D structures|Epidermal growth factor receptor 3D structures]]
-
 
+
== References ==
-
==Reference==
+
<references/>
-
<ref group="xtra">PMID:019289842</ref><references group="xtra"/>
+
__TOC__
 +
</StructureSection>
 +
[[Category: Homo sapiens]]
 +
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
-
[[Category: Burgess, A W.]]
+
[[Category: Burgess AW]]
-
[[Category: Garrett, T P.J.]]
+
[[Category: Garrett TPJ]]
-
[[Category: Huyton, T.]]
+
[[Category: Huyton T]]
-
[[Category: Xu, Y.]]
+
[[Category: Xu Y]]
-
[[Category: Antibody]]
+
-
[[Category: Immune system]]
+

Current revision

Antibodies Specifically Targeting a Locally Misfolded Region of Tumor Associated EGFR

PDB ID 3g5v

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/3g5v"
Personal tools