View source for 6nk2


==EphA2 LBD in complex with bA-WLA-YRPK bio peptide==
<StructureSection load='6nk2' size='340' side='right'caption='[[6nk2]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6nk2]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NK2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NK2 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BAL:BETA-ALANINE'>BAL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=6nk2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nk2 OCA], [https://pdbe.org/6nk2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nk2 RCSB], [https://www.ebi.ac.uk/pdbsum/6nk2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nk2 ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
The EPH receptor A2 (EphA2) receptor tyrosine kinase plays an important role in a plethora of biological and disease processes, ranging from angiogenesis and cancer to inflammation and parasitic infections. EphA2 is therefore considered an important drug target. Two short peptides previously identified by phage display, named YSA and SWL, are widely used as EphA2-targeting agents owing to their high specificity for this receptor. However, these peptides have only modest (micromolar) potency. Lack of structural information on the binding interactions of YSA and SWL with the extracellular EphA2 ligand-binding domain (LBD) has for many years precluded structure-guided improvements. We now report the high-resolution (1.53-2.20 A) crystal structures of the YSA peptide and several of its improved derivatives in complex with the EphA2 LBD, disclosing that YSA targets the ephrin-binding pocket of EphA2 and mimics binding features of the ephrin-A ligands. The structural information obtained enabled iterative peptide modifications conferring low nanomolar potency. Furthermore, contacts observed in the crystal structures shed light on how C-terminal features can convert YSA derivatives from antagonists to agonists that likely bivalently interact with two EphA2 molecules to promote receptor oligomerization, autophosphorylation, and downstream signaling. Consistent with this model, quantitative FRET measurements in live cells revealed that the peptide agonists promote the formation of EphA2 oligomeric assemblies. Our findings now enable rational strategies to differentially modify EphA2 signaling toward desired outcomes by using appropriately engineered peptides. Such peptides could be used as research tools to interrogate EphA2 function and develop pharmacological leads.

Engineering Nanomolar Peptide LigandsThat Differentially Modulate EphA2 Receptor Signaling.,Gomez-Soler M, Petersen Gehring M, Lechtenberg BC, Zapata-Mercado E, Hristova K, Pasquale EB J Biol Chem. 2019 Apr 23. pii: RA119.008213. doi: 10.1074/jbc.RA119.008213. PMID:31015204<ref>PMID:31015204</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6nk2" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ephrin receptor 3D structures|Ephrin receptor 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Lechtenberg BC]]
[[Category: Pasquale EB]]