3qwq

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (02:20, 21 November 2024) (edit) (undo)
 
(4 intermediate revisions not shown.)
Line 1: Line 1:
-
{{STRUCTURE_3qwq| PDB=3qwq | SCENE= }}
 
-
===Crystal structure of the extracellular domain of the epidermal growth factor receptor in complex with an adnectin===
 
-
{{ABSTRACT_PUBMED_22325775}}
 
-
==Disease==
+
==Crystal structure of the extracellular domain of the epidermal growth factor receptor in complex with an adnectin==
-
[[http://www.uniprot.org/uniprot/EGFR_HUMAN EGFR_HUMAN]] Defects in EGFR are associated with lung cancer (LNCR) [MIM:[http://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.
+
<StructureSection load='3qwq' size='340' side='right'caption='[[3qwq]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[3qwq]] is a 2 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=3QWQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QWQ 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]] 2.75&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=3qwq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qwq OCA], [https://pdbe.org/3qwq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qwq RCSB], [https://www.ebi.ac.uk/pdbsum/3qwq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qwq 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>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Adnectins are targeted biologics derived from the tenth type III domain of human fibronectin ((10)Fn3), a member of the immunoglobulin superfamily. Target-specific binders are selected from libraries generated by diversifying the three (10)Fn3 loops that are analogous to the complementarity determining regions of antibodies. The crystal structures of two Adnectins were determined, each in complex with its therapeutic target, EGFR or IL-23. Both Adnectins bind different epitopes than those bound by known monoclonal antibodies. Molecular modeling suggests that some of these epitopes might not be accessible to antibodies because of the size and concave shape of the antibody combining site. In addition to interactions from the Adnectin diversified loops, residues from the N terminus and/or the beta strands interact with the target proteins in both complexes. Alanine-scanning mutagenesis confirmed the calculated binding energies of these beta strand interactions, indicating that these nonloop residues can expand the available binding footprint.
-
==Function==
+
Structures of adnectin/protein complexes reveal an expanded binding footprint.,Ramamurthy V, Krystek SR Jr, Bush A, Wei A, Emanuel SL, Das Gupta R, Janjua A, Cheng L, Murdock M, Abramczyk B, Cohen D, Lin Z, Morin P, Davis JH, Dabritz M, McLaughlin DC, Russo KA, Chao G, Wright MC, Jenny VA, Engle LJ, Furfine E, Sheriff S Structure. 2012 Feb 8;20(2):259-69. PMID:22325775<ref>PMID:22325775</ref>
-
[[http://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>
+
-
==About this Structure==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[3qwq]] is a 2 chain structure 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=3QWQ OCA].
+
</div>
 +
<div class="pdbe-citations 3qwq" style="background-color:#fffaf0;"></div>
-
==Reference==
+
==See Also==
-
<ref group="xtra">PMID:022325775</ref><references group="xtra"/><references/>
+
*[[Epidermal growth factor receptor 3D structures|Epidermal growth factor receptor 3D structures]]
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Receptor protein-tyrosine kinase]]
+
[[Category: Large Structures]]
-
[[Category: Sheriff, S.]]
+
[[Category: Sheriff S]]
-
[[Category: Adnectin]]
+
-
[[Category: Antibody mimic]]
+
-
[[Category: Antitumor]]
+
-
[[Category: Cell surface receptor]]
+
-
[[Category: Drug]]
+
-
[[Category: Engineered binding protein]]
+
-
[[Category: Glycoprotein]]
+
-
[[Category: Protein binding-signaling protein complex]]
+
-
[[Category: Signaling protein]]
+
-
[[Category: Tyrosine kinase]]
+

Current revision

Crystal structure of the extracellular domain of the epidermal growth factor receptor in complex with an adnectin

PDB ID 3qwq

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/3qwq"
Personal tools