3J3O

Conformational Shift of a Major Poliovirus Antigen Confirmed by Immuno-Cryogenic Electron Microscopy: 160S Poliovirus and C3-Fab Complex

Summary for 3J3O

• Entry DOI: 10.2210/pdb3j3o/pdb
• Related: 3J3P
• EMDB information: 5291 5292 5293
• Descriptor: C3 antibody, light chain, C3 antibody, heavy chain, unknown peptide, ... (9 entities in total)
• Functional Keywords: antibody-antigen interaction, antibody-protein interaction, picornavirus, virus-antibody interaction, neutralizing antibody interaction, conformational change, virus-immune system complex, virus/immune system
• Biological source: Mus musculus (mouse); More
• Total number of polymer chains: 7
• Total formula weight: 146029.08

Authors

Lin, J.,Cheng, N.,Hogle, J.M.,Steven, A.C.,Belnap, D.M. (deposition date: 2013-04-10, release date: 2013-07-03, Last modification date: 2024-02-21)

Primary citation

Lin, J.,Cheng, N.,Hogle, J.M.,Steven, A.C.,Belnap, D.M.
Conformational shift of a major poliovirus antigen confirmed by immuno-cryogenic electron microscopy.
J.Immunol., 191:884-891, 2013

PubMed Abstract: Small, interfacial conformational changes occur in some Ag-Ab interactions. Using cryogenic electron microscopy (cryo-EM), we have demonstrated such changes in a major antigenic site of a poliovirus capsid protein. During cell entry, native human poliovirus (160S particle) converts to a cell entry intermediate (135S particle) and later to an RNA-released (80S) particle. By mixing particles with Fabs of the neutralizing C3 mAb, we labeled the external loop connecting the B and C β-strands (BC loop) of the capsid protein VP1 (residues 95-105) in the 160S and 135S states. We then determined three-dimensional structures by cryo-EM and enhanced their interpretability by fitting high-resolution coordinates of C3 Fab and the capsid proteins into the density maps. Binding of C3 to either 160S or 135S particles caused residues of the BC loop, located on the tip of a prominent peak known as the "mesa," to move by an estimated 5 Å. C3 Abs are neutralizing and can bind bivalently. The orientation of the bound Fabs in our reconstructions suggests that C3 neutralizes poliovirus by binding two adjacent BC loops on the same mesa and inhibiting conformational changes in the viral capsid.

PubMed: 23772035
DOI: 10.4049/jimmunol.1202014

Experimental method

ELECTRON MICROSCOPY (11.1 Å)