Structural highlights
Function
[Q6DLV0_9FLAV] Envelope protein E binding to host cell surface receptor is followed by virus internalization through clathrin-mediated endocytosis. Envelope protein E is subsequently involved in membrane fusion between virion and host late endosomes. Synthesized as a homodimer with prM which acts as a chaperone for envelope protein E. After cleavage of prM, envelope protein E dissociate from small envelope protein M and homodimerizes (By similarity).[SAAS:SAAS000336_004_099774]
Publication Abstract from PubMed
Dengue virus (DENV) infects ~400 million people annually. There is no licensed vaccine or therapeutic drug. Only a small fraction of the total DENV-specific antibodies in a naturally occurring dengue infection consists of highly neutralizing antibodies. Here we show that the DENV-specific human monoclonal antibody 5J7 is exceptionally potent, neutralizing 50% of virus at nanogram-range antibody concentration. The 9 A resolution cryo-electron microscopy structure of the Fab 5J7-DENV complex shows that a single Fab molecule binds across three envelope proteins and engages three functionally important domains, each from a different envelope protein. These domains are critical for receptor binding and fusion to the endosomal membrane. The ability to bind to multiple domains allows the antibody to fully coat the virus surface with only 60 copies of Fab, that is, half the amount compared with other potent antibodies. Our study reveals a highly efficient and unusual mechanism of molecular recognition by an antibody.
A highly potent human antibody neutralizes dengue virus serotype 3 by binding across three surface proteins.,Fibriansah G, Tan JL, Smith SA, de Alwis R, Ng TS, Kostyuchenko VA, Jadi RS, Kukkaro P, de Silva AM, Crowe JE, Lok SM Nat Commun. 2015 Feb 20;6:6341. doi: 10.1038/ncomms7341. PMID:25698059[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Fibriansah G, Tan JL, Smith SA, de Alwis R, Ng TS, Kostyuchenko VA, Jadi RS, Kukkaro P, de Silva AM, Crowe JE, Lok SM. A highly potent human antibody neutralizes dengue virus serotype 3 by binding across three surface proteins. Nat Commun. 2015 Feb 20;6:6341. doi: 10.1038/ncomms7341. PMID:25698059 doi:http://dx.doi.org/10.1038/ncomms7341
