4cbf | pdb_00004cbf
Near-atomic resolution cryo-EM structure of Dengue serotype 4 virus
Structural highlights
FunctionE0WXI2_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:SAAS011998_004_099774] Publication Abstract from PubMedDengue virus (DENV), a mosquito-borne virus, is responsible for millions cases of infections worldwide. There are four DENV serotypes (DENV1 - 4). After a primary DENV infection, the antibodies elicited confer lifetime protection against that DENV serotype. However, in a secondary infection with another serotype, the pre-existing antibodies may cause antibody-dependent enhancement (ADE) of infection of macrophage cells leading to the development of the more severe form of disease, dengue hemorrhagic fever. Thus a safe vaccine should stimulate protection against all dengue serotypes simultaneously. To facilitate the development of a vaccine, good knowledge of different DENV serotype structures is crucial. Structures of DENV1 and DENV2 had been solved previously. Here we present a near-atomic resolution cryo-electron microscopy (cryo-EM) structure of mature DENV4. Comparison of the DENV4 structure with similar resolution cryo-EM structures of DENV1 and DENV2 showed differences in surface charge distribution, which may explain their differences in binding to cellular receptors such as heparin. Also, observed variations in amino acid residues involved in interactions between envelope and membrane proteins on the virus surface correlate with their ability to undergo structural changes at higher temperatures. Near-atomic resolution cryo-EM structure of Dengue serotype 4 virus.,Kostyuchenko VA, Chew PL, Ng TS, Lok SM J Virol. 2013 Oct 23. PMID:24155405[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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