View source for 6adr


==Anthrax Toxin Receptor 1-bound the Seneca Valley Virus in neutral conditions==
<SX load='6adr' size='340' side='right' viewer='molstar' caption='[[6adr]], [[Resolution|resolution]] 3.38&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6adr]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Senecavirus_A Senecavirus A]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ADR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ADR FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.38&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=6adr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6adr OCA], [https://pdbe.org/6adr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6adr RCSB], [https://www.ebi.ac.uk/pdbsum/6adr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6adr ProSAT]</span></td></tr>
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== Disease ==
[https://www.uniprot.org/uniprot/ANTR1_HUMAN ANTR1_HUMAN] Defects in ANTXR1 are associated with susceptibility to hemangioma capillary infantile (HCI) [MIM:[https://omim.org/entry/602089 602089]. HCI are benign, highly proliferative lesions involving aberrant localized growth of capillary endothelium. They are the most common tumor of infancy, occurring in up to 10% of all births. Hemangiomas tend to appear shortly after birth and show rapid neonatal growth for up to 12 months characterized by endothelial hypercellularity and increased numbers of mast cells. This phase is followed by slow involution at a rate of about 10% per year and replacement by fibrofatty stroma.<ref>PMID:18931684</ref> 
== Function ==
[https://www.uniprot.org/uniprot/ANTR1_HUMAN ANTR1_HUMAN] Plays a role in cell attachment and migration. Interacts with extracellular matrix proteins and with the actin cytoskeleton. Mediates adhesion of cells to type 1 collagen and gelatin, reorganization of the actin cytoskeleton and promotes cell spreading. Plays a role in the angiogenic response of cultured umbilical vein endothelial cells.<ref>PMID:15777794</ref> <ref>PMID:16762926</ref> 
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== Publication Abstract from PubMed ==
Seneca Valley virus (SVV) is an oncolytic picornavirus with selective tropism for neuroendocrine cancers. SVV mediates cell entry by attachment to the receptor anthrax toxin receptor 1 (ANTXR1). Here we determine atomic structures of mature SVV particles alone and in complex with ANTXR1 in both neutral and acidic conditions, as well as empty "spent" particles in complex with ANTXR1 in acidic conditions by cryoelectron microscopy. SVV engages ANTXR1 mainly by the VP2 DF and VP1 CD loops, leading to structural changes in the VP1 GH loop and VP3 GH loop, which attenuate interprotomer interactions and destabilize the capsid assembly. Despite lying on the edge of the attachment site, VP2 D146 interacts with the metal ion in ANTXR1 and is required for cell entry. Though the individual substitution of most interacting residues abolishes receptor binding and virus propagation, a serine-to-alanine mutation at VP2 S177 significantly increases SVV proliferation. Acidification of the SVV-ANTXR1 complex results in a major reconfiguration of the pentameric capsid assemblies, which rotate approximately 20 degrees around the icosahedral fivefold axes to form a previously uncharacterized spent particle resembling a potential uncoating intermediate with remarkable perforations at both two- and threefold axes. These structures provide high-resolution snapshots of SVV entry, highlighting opportunities for anticancer therapeutic optimization.

Seneca Valley virus attachment and uncoating mediated by its receptor anthrax toxin receptor 1.,Cao L, Zhang R, Liu T, Sun Z, Hu M, Sun Y, Cheng L, Guo Y, Fu S, Hu J, Li X, Yu C, Wang H, Chen H, Li X, Fry EE, Stuart DI, Qian P, Lou Z, Rao Z Proc Natl Acad Sci U S A. 2018 Dec 18;115(51):13087-13092. doi:, 10.1073/pnas.1814309115. Epub 2018 Dec 4. PMID:30514821<ref>PMID:30514821</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 6adr" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Senecavirus A]]
[[Category: Cao L]]
[[Category: Lou ZY]]