6adm

Anthrax Toxin Receptor 1-bound full particles of Seneca Valley Virus in acidic conditions

Loading... Status: waiting for Mol* initialization Structural highlights 6adm is a 5 chain structure with sequence from Homo sapiens and Senecavirus A. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.84Å Ligands: MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A1U9IRU2_9PICO 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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