3skj

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{{STRUCTURE_3skj| PDB=3skj | SCENE= }}
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==Structural And Functional Characterization of an Agonistic Anti-Human EphA2 Monoclonal Antibody==
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===Structural And Functional Characterization of an Agonistic Anti-Human EphA2 Monoclonal Antibody===
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<StructureSection load='3skj' size='340' side='right' caption='[[3skj]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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{{ABSTRACT_PUBMED_21867711}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3skj]] is a 6 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=3SKJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SKJ FirstGlance]. <br>
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</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EPHA2, ECK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3skj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3skj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3skj RCSB], [http://www.ebi.ac.uk/pdbsum/3skj PDBsum]</span></td></tr>
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</table>
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== Disease ==
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[[http://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:[http://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:[http://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>
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== Function ==
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[[http://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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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We report here the three-dimensional structure of human ephrin type A receptor 2 (EphA2) bound to the Fab (fragment antigen binding) of an agonistic human antibody (1C1; IgG1/kappa). The structure of the corresponding complex was solved at a resolution of 2.5 A using molecular replacement and constitutes the first reported structure of a human ephrin receptor bound to an antibody. We have also defined the corresponding functional epitope using a mutagenesis-based approach. This study revealed discrete structural features that determine the fine specificity of 1C1 to EphA2. Our data also provided a molecular basis for 1C1 mechanism of action. More precisely, we propose that its agonistic, internalizing properties are the result of ligand mimicry by the third heavy-chain complementarity-determining region of 1C1. Because EphA2 is an important contributor to cancer formation and progression, these findings may have implications for designing the next generation of anti-tumor therapies.
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==Disease==
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Structural and Functional Characterization of an Agonistic Anti-Human EphA2 Monoclonal Antibody.,Peng L, Oganesyan V, Damschroder MM, Wu H, Dall'acqua WF J Mol Biol. 2011 Aug 16. PMID:21867711<ref>PMID:21867711</ref>
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[[http://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:[http://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:[http://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>
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==Function==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[http://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>
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</div>
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==About this Structure==
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[[3skj]] is a 6 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=3SKJ OCA].
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==See Also==
==See Also==
*[[Antibody|Antibody]]
*[[Antibody|Antibody]]
*[[Monoclonal Antibody|Monoclonal Antibody]]
*[[Monoclonal Antibody|Monoclonal Antibody]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:021867711</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Receptor protein-tyrosine kinase]]
[[Category: Receptor protein-tyrosine kinase]]
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[[Category: Acqua, W F.Dall.]]
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[[Category: Acqua, W F.Dall]]
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[[Category: Oganesyan, V Y.]]
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[[Category: Oganesyan, V Y]]
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[[Category: Wu, H.]]
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[[Category: Wu, H]]
[[Category: Antibody]]
[[Category: Antibody]]
[[Category: Antigen]]
[[Category: Antigen]]

Revision as of 07:08, 21 December 2014

Structural And Functional Characterization of an Agonistic Anti-Human EphA2 Monoclonal Antibody

3skj, resolution 2.50Å

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