6cx1
From Proteopedia
Cryo-EM structure of Seneca Valley Virus-Anthrax Toxin Receptor 1 complex
Structural highlights
Disease[ANTR1_HUMAN] Defects in ANTXR1 are associated with susceptibility to hemangioma capillary infantile (HCI) [MIM: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.[1] Function[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.[2] [3] Publication Abstract from PubMedRecently, the use of oncolytic viruses in cancer therapy has become a realistic therapeutic option. Seneca Valley Virus (SVV) is a newly discovered picornavirus, which has earned a significant reputation as a potent oncolytic agent. Anthrax toxin receptor 1 (ANTXR1), one of the cellular receptors for the protective antigen secreted by Bacillus anthracis, has been identified as the high-affinity cellular receptor for SVV. Here, we report the structure of the SVV-ANTXR1 complex determined by single-particle cryo-electron microscopy analysis at near-atomic resolution. This is an example of a shared receptor structure between a mammalian virus and a bacterial toxin. Our structure shows that ANTXR1 decorates the outer surface of the SVV capsid and interacts with the surface-exposed BC loop and loop II of VP1, "the puff" of VP2 and "the knob" of VP3. Comparison of the receptor-bound capsid structure with the native capsid structure reveals that receptor binding induces minor conformational changes in SVV capsid structure, suggesting the role of ANTXR1 as an attachment receptor. Furthermore, our results demonstrate that the capsid footprint on the receptor is not conserved in anthrax toxin receptor 2 (ANTXR2), thereby providing a molecular mechanism for explaining the exquisite selectivity of SVV for ANTXR1. Structural basis for anthrax toxin receptor 1 recognition by Seneca Valley Virus.,Jayawardena N, Burga LN, Easingwood RA, Takizawa Y, Wolf M, Bostina M Proc Natl Acad Sci U S A. 2018 Nov 13;115(46):E10934-E10940. doi:, 10.1073/pnas.1810664115. Epub 2018 Oct 31. PMID:30381454[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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