5BQ7

Crystal structure of chikungunya virus-human Fab 5F-10 fragment

Summary for 5BQ7

• Entry DOI: 10.2210/pdb5bq7/pdb
• Descriptor: Fab 5F-10-Heavy Chain, Fab 5F-10-Light Chain, DI(HYDROXYETHYL)ETHER, ... (4 entities in total)
• Functional Keywords: human antibody fab fragment, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 50572.56

Authors

Mangala Prasad, V.,Rossmann, M.G. (deposition date: 2015-05-28, release date: 2015-11-18, Last modification date: 2023-09-27)

Primary citation

Porta, J.,Mangala Prasad, V.,Wang, C.I.,Akahata, W.,Ng, L.F.,Rossmann, M.G.
Structural Studies of Chikungunya Virus-Like Particles Complexed with Human Antibodies: Neutralization and Cell-to-Cell Transmission.
J.Virol., 90:1169-1177, 2015

PubMed Abstract: Chikungunya virus is a positive-stranded RNA alphavirus. Structures of chikungunya virus-like particles in complex with strongly neutralizing antibody Fab fragments (8B10 and 5F10) were determined using cryo-electron microscopy and X-ray crystallography. By fitting the crystallographically determined structures of these Fab fragments into the cryo-electron density maps, we show that Fab fragments of antibody 8B10 extend radially from the viral surface and block receptor binding on the E2 glycoprotein. In contrast, Fab fragments of antibody 5F10 bind the tip of the E2 B domain and lie tangentially on the viral surface. Fab 5F10 fixes the B domain rigidly to the surface of the virus, blocking exposure of the fusion loop on glycoprotein E1 and therefore preventing the virus from becoming fusogenic. Although Fab 5F10 can neutralize the wild-type virus, it can also bind to a mutant virus without inhibiting fusion or attachment. Although the mutant virus is no longer able to propagate by extracellular budding, it can, however, enter the next cell by traveling through junctional complexes without being intercepted by a neutralizing antibody to the wild-type virus, thus clarifying how cell-to-cell transmission can occur.

PubMed: 26537684
DOI: 10.1128/JVI.02364-15

Experimental method

X-RAY DIFFRACTION (2.738 Å)