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TitleUnexpected mode of engagement between enterovirus 71 and its receptor SCARB2.
Journal, issue, pagesNat Microbiol, Vol. 4, Issue 3, Page 414-419, Year 2019
Publish dateDec 10, 2018
AuthorsDaming Zhou / Yuguang Zhao / Abhay Kotecha / Elizabeth E Fry / James T Kelly / Xiangxi Wang / Zihe Rao / David J Rowlands / Jingshan Ren / David I Stuart /
PubMed AbstractEnterovirus 71 (EV71) is a common cause of hand, foot and mouth disease-a disease endemic especially in the Asia-Pacific region. Scavenger receptor class B member 2 (SCARB2) is the major receptor of ...Enterovirus 71 (EV71) is a common cause of hand, foot and mouth disease-a disease endemic especially in the Asia-Pacific region. Scavenger receptor class B member 2 (SCARB2) is the major receptor of EV71, as well as several other enteroviruses responsible for hand, foot and mouth disease, and plays a key role in cell entry. The isolated structures of EV71 and SCARB2 are known, but how they interact to initiate infection is not. Here, we report the EV71-SCARB2 complex structure determined at 3.4 Å resolution using cryo-electron microscopy. This reveals that SCARB2 binds EV71 on the southern rim of the canyon, rather than across the canyon, as predicted. Helices 152-163 (α5) and 183-193 (α7) of SCARB2 and the viral protein 1 (VP1) GH and VP2 EF loops of EV71 dominate the interaction, suggesting an allosteric mechanism by which receptor binding might facilitate the low-pH uncoating of the virus in the endosome/lysosome. Remarkably, many residues within the binding footprint are not conserved across SCARB2-dependent enteroviruses; however, a conserved proline and glycine seem to be key residues. Thus, although the virus maintains antigenic variability even within the receptor-binding footprint, the identification of binding 'hot spots' may facilitate the design of receptor mimic therapeutics less likely to quickly generate resistance.
External linksNat Microbiol / PubMed:30531980
MethodsEM (single particle)
Resolution3.4 Å
Structure data

EMDB-0332, PDB-6i2k:
Structure of EV71 complexed with its receptor SCARB2
Method: EM (single particle) / Resolution: 3.4 Å

Chemicals

ChemComp-906:
1-(2-aminopyridin-4-yl)-3-[(3S)-5-{4-[(E)-(ethoxyimino)methyl]phenoxy}-3-methylpentyl]imidazolidin-2-one

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • homo sapiens (human)
  • enterovirus a71
KeywordsVIRUS / Enterovirus 71 / SCARB2 / Hand-foot-mouth disease / EV71 receptor

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