3JD7

The novel asymmetric entry intermediate of a picornavirus captured with nanodiscs

Summary for 3JD7

• Entry DOI: 10.2210/pdb3jd7/pdb
• EMDB information: 6636 6637 6638
• Descriptor: Capsid protein VP1, Capsid protein VP2, Capsid protein VP3, ... (5 entities in total)
• Functional Keywords: picornavirus, entry intermediate, virus
• Biological source: Coxsackievirus B3; More
• Cellular location: Capsid protein VP0: Virion . Capsid protein VP4: Virion . Capsid protein VP2: Virion . Capsid protein VP3: Virion . Capsid protein VP1: Virion . Protein 2B: Host cytoplasmic vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side . Protein 2C: Host cytoplasmic vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side . Protein 3A: Host cytoplasmic vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side . Protein 3AB: Host cytoplasmic vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side . Viral protein genome-linked: Virion . Protease 3C: Host cytoplasm . Protein 3CD: Host cytoplasmic vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side . RNA-directed RNA polymerase: Host cytoplasmic vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side : Q66282 Q66282 Q66282 Q66282
• Total number of polymer chains: 4
• Total formula weight: 94091.83

Authors

Lee, H.,Shingler, K.L.,Organtini, L.J.,Ashley, R.E.,Makhov, A.M.,Conway, J.F.,Hafenstein, S. (deposition date: 2016-04-29, release date: 2016-09-14, Last modification date: 2024-02-21)

Primary citation

Lee, H.,Shingler, K.L.,Organtini, L.J.,Ashley, R.E.,Makhov, A.M.,Conway, J.F.,Hafenstein, S.
The novel asymmetric entry intermediate of a picornavirus captured with nanodiscs.
Sci Adv, 2:e1501929-e1501929, 2016

PubMed Abstract: 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.

PubMed: 27574701
DOI: 10.1126/sciadv.1501929

Experimental method

ELECTRON MICROSCOPY (3.9 Å)