View source for 7czf


==Crystal structure of Kaposi Sarcoma associated herpesvirus (KSHV ) gHgL in complex with the ligand binding domian (LBD) of EphA2==
<StructureSection load='7czf' size='340' side='right'caption='[[7czf]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7czf]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_gammaherpesvirus_8 Human gammaherpesvirus 8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CZF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CZF 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]] 3.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=7czf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7czf OCA], [https://pdbe.org/7czf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7czf RCSB], [https://www.ebi.ac.uk/pdbsum/7czf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7czf ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/EPHA2_HUMAN EPHA2_HUMAN] Genetic variations in EPHA2 are the cause of susceptibility to cataract cortical age-related type 2 (ARCC2) [MIM:[https://omim.org/entry/613020 613020]. A developmental punctate opacity common in the cortex and present in most lenses. The cataract is white or cerulean, increases in number with age, but rarely affects vision.<ref>PMID:19573808</ref> <ref>PMID:19649315</ref>   Defects in EPHA2 are the cause of cataract posterior polar type 1 (CTPP1) [MIM:[https://omim.org/entry/116600 116600]. A subcapsular opacity, usually disk-shaped, located at the back of the lens. It can have a marked effect on visual acuity.<ref>PMID:19573808</ref> <ref>PMID:19005574</ref> <ref>PMID:19306328</ref> <ref>PMID:22570727</ref>   Note=Overexpressed in several cancer types and promotes malignancy.<ref>PMID:19573808</ref> 
== Function ==
[https://www.uniprot.org/uniprot/EPHA2_HUMAN EPHA2_HUMAN] Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand-independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis.<ref>PMID:10655584</ref> <ref>PMID:16236711</ref> <ref>PMID:18339848</ref> <ref>PMID:19573808</ref> <ref>PMID:20679435</ref> <ref>PMID:20861311</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The human gamma-herpesviruses Kaposi sarcoma associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are associated with many human malignancies. Viral glycoprotein H (gH) and glycoprotein L (gL) are crucial for the cell tropism by binding to specific receptors. Recently, EphA2 was identified as the specific entry receptor for both KSHV and EBV. Here, we characterized the crystal structures of KSHV gHgL or EBV gHgL in complex with the ligand binding domain (LBD) of EphA2. Both KSHV and EBV gHgL bind to the channel and peripheral regions of LBD primarily using gL. Extensive interactions with more contacts contribute to the higher affinity of KSHV gHgL to LBD than that of EBV gHgL. These binding characteristics were verified using cell-based fusion assays with mutations in key EphA2 residues. Our experiments suggest that multiple animal gamma-herpesviruses could use EphA2 as an entry receptor, implying a potential threat to human health.

Molecular basis of EphA2 recognition by gHgL from gammaherpesviruses.,Su C, Wu L, Chai Y, Qi J, Tan S, Gao GF, Song H, Yan J Nat Commun. 2020 Nov 24;11(1):5964. doi: 10.1038/s41467-020-19617-9. PMID:33235207<ref>PMID:33235207</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7czf" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ephrin receptor 3D structures|Ephrin receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Human gammaherpesvirus 8]]
[[Category: Large Structures]]
[[Category: Chai Y]]
[[Category: Gao GF]]
[[Category: Qi JX]]
[[Category: Song H]]
[[Category: Su C]]
[[Category: Wu LL]]
[[Category: Yan JH]]