View source for 6f7m


==NMR structure of EphA2-Sam stapled peptides (S13ST)==
<StructureSection load='6f7m' size='340' side='right'caption='[[6f7m]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6f7m]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6F7M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6F7M FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=MK8:2-METHYL-L-NORLEUCINE'>MK8</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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=6f7m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6f7m OCA], [https://pdbe.org/6f7m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6f7m RCSB], [https://www.ebi.ac.uk/pdbsum/6f7m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6f7m 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 ==
Sam (Sterile alpha motif) domains represent small helical protein-protein interaction modules which play versatile functions in different cellular processes. The Sam domain from the EphA2 receptor binds the Sam domain of the lipid phosphatase Ship2 and this interaction modulates receptor endocytosis and degradation primarily generating pro-oncogenic effects in cell. To identify molecule antagonists of the EphA2-Sam/Ship2-Sam complex with anti-cancer activity, we focused on hydrocarbon helical stapled peptides. EphA2-Sam and one of its interactors (i.e., the first Sam domain of the adaptor protein Odin) were used as model systems for peptide design. Increase in helicity in the stapled peptides, with respect to the corresponding linear/native-like regions, was proved by structural studies conducted through CD (Circular Dichroism) and NMR (Nuclear Magnetic Resonance). Interestingly, interaction assays by means of NMR, SPR (Surface Plasmon Resonance) and MST (MicroScale Thermophoresis) techniques led to the discovery of a novel ligand of Ship2-Sam.

Sam domain-based stapled peptides: Structural analysis and interaction studies with the Sam domains from the EphA2 receptor and the lipid phosphatase Ship2.,Mercurio FA, Pirone L, Di Natale C, Marasco D, Pedone EM, Leone M Bioorg Chem. 2018 Jul 20;80:602-610. doi: 10.1016/j.bioorg.2018.07.013. PMID:30036816<ref>PMID:30036816</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6f7m" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ephrin receptor 3D structures|Ephrin receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Leone M]]
[[Category: Mercurio FA]]