6I2K

Structure of EV71 complexed with its receptor SCARB2

Summary for 6I2K

• Entry DOI: 10.2210/pdb6i2k/pdb
• EMDB information: 0332
• Descriptor: Polyprotein, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 1-(2-aminopyridin-4-yl)-3-[(3S)-5-{4-[(E)-(ethoxyimino)methyl]phenoxy}-3-methylpentyl]imidazolidin-2-one, ... (12 entities in total)
• Functional Keywords: enterovirus 71, scarb2, hand-foot-mouth disease, ev71 receptor, virus
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 147035.46

Authors

Zhou, D.,Zhao, Y.,Kotecha, A.,Fry, E.E.,Kelly, J.,Wang, X.,Rao, Z.,Rowlands, D.J.,Ren, J.,Stuart, D.I. (deposition date: 2018-11-01, release date: 2018-11-28, Last modification date: 2024-11-20)

Primary citation

Zhou, D.,Zhao, Y.,Kotecha, A.,Fry, E.E.,Kelly, J.T.,Wang, X.,Rao, Z.,Rowlands, D.J.,Ren, J.,Stuart, D.I.
Unexpected mode of engagement between enterovirus 71 and its receptor SCARB2.
Nat Microbiol, 4:414-419, 2019

PubMed Abstract: 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.

PubMed: 30531980
DOI: 10.1038/s41564-018-0319-z

Experimental method

ELECTRON MICROSCOPY (3.4 Å)