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TitleThe novel asymmetric entry intermediate of a picornavirus captured with nanodiscs.
Journal, issue, pagesSci Adv, Vol. 2, Issue 8, Page e1501929, Year 2016
Publish dateAug 24, 2016
AuthorsHyunwook Lee / Kristin L Shingler / Lindsey J Organtini / Robert E Ashley / Alexander M Makhov / James F Conway / Susan Hafenstein /
PubMed AbstractMany nonenveloped viruses engage host receptors that initiate capsid conformational changes necessary for genome release. Structural studies on the mechanisms of picornavirus entry have relied on in ...Many nonenveloped viruses engage host receptors that initiate capsid conformational changes necessary for genome release. Structural studies on the mechanisms of picornavirus entry have relied on in vitro approaches of virus incubated at high temperatures or with excess receptor molecules to trigger the entry intermediate or A-particle. We have induced the coxsackievirus B3 entry intermediate by triggering the virus with full-length receptors embedded in lipid bilayer nanodiscs. These asymmetrically formed A-particles were reconstructed using cryo-electron microscopy and a direct electron detector. These first high-resolution structures of a picornavirus entry intermediate captured at a membrane with and without imposing icosahedral symmetry (3.9 and 7.8 Å, respectively) revealed a novel A-particle that is markedly different from the classical A-particles. The asymmetric receptor binding triggers minimal global capsid expansion but marked local conformational changes at the site of receptor interaction. In addition, viral proteins extrude from the capsid only at the site of extensive protein remodeling adjacent to the nanodisc. Thus, the binding of the receptor triggers formation of a unique site in preparation for genome release.
External linksSci Adv / PubMed:27574701 / PubMed Central
MethodsEM (single particle)
Resolution3.9 - 7.8 Å
Structure data

EMDB-6636:
The novel asymmetric entry intermediate of a picornavirus captured with nanodiscs
Method: EM (single particle) / Resolution: 3.9 Å

6637

3jd7

EMDB-6637, PDB-3jd7:
The novel asymmetric entry intermediate of a picornavirus captured with nanodiscs
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-6638:
The novel asymmetric entry intermediate of a picornavirus captured with nanodiscs
Method: EM (single particle) / Resolution: 7.8 Å

Chemicals

ChemComp-PLM:
PALMITIC ACID / Palmitic acid

Source
  • coxsackievirus b3
KeywordsVIRUS / picornavirus / entry intermediate

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