3UYP

Crystal structure of the dengue virus serotype 4 envelope protein domain III in complex with the variable domains of Mab 4E11

Summary for 3UYP

• Entry DOI: 10.2210/pdb3uyp/pdb
• Related: 3UZE 3UZQ 3UZV
• Descriptor: anti-dengue Mab 4E11, Envelope protein, GLYCEROL, ... (6 entities in total)
• Functional Keywords: dengue antibody neutralization, immune system
• Biological source: Mus musculus (mouse); More
• Cellular location: Envelope protein E: Virion membrane; Multi- pass membrane protein: Q9IZJ0
• Total number of polymer chains: 2
• Total formula weight: 40587.26

Authors

Cockburn, J.J.B.,Navarro Sanchez, M.E.,Fretes, N.,Urvoas, A.,Staropoli, I.,Kikuti, C.M.,Coffey, L.L.,Arenzana Seisdedos, F.,Bedouelle, H.,Rey, F.A. (deposition date: 2011-12-06, release date: 2012-02-22, Last modification date: 2024-11-20)

Primary citation

Cockburn, J.J.,Navarro Sanchez, M.E.,Fretes, N.,Urvoas, A.,Staropoli, I.,Kikuti, C.M.,Coffey, L.L.,Arenzana Seisdedos, F.,Bedouelle, H.,Rey, F.A.
Mechanism of dengue virus broad cross-neutralization by a monoclonal antibody.
Structure, 20:303-314, 2012

PubMed Abstract: The dengue virus (DENV) complex is composed of four distinct but serologically related flaviviruses, which together cause the present-day most important emerging viral disease. Although DENV infection induces lifelong immunity against viruses of the same serotype, the antibodies raised appear to contribute to severe disease in cases of heterotypic infections. Understanding the mechanisms of DENV neutralization by antibodies is, therefore, crucial for the design of vaccines that simultaneously protect against all four viruses. Here, we report a comparative, high-resolution crystallographic analysis of an "A-strand" murine monoclonal antibody, Mab 4E11, in complex with its target domain of the envelope protein from the four DENVs. Mab 4E11 is capable of neutralizing all four serotypes, and our study reveals the determinants of this cross-reactivity. The structures also highlight the mechanism by which A-strand Mabs disrupt the architecture of the mature virion, inducing premature fusion loop exposure and concomitant particle inactivation.

PubMed: 22285214
DOI: 10.1016/j.str.2012.01.001

Experimental method

X-RAY DIFFRACTION (2 Å)