3j42
Obstruction of Dengue Virus Maturation by Fab Fragments of the 2H2 Antibody
Structural highlights
FunctionO11875_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:SAAS026470_004_099774] Publication Abstract from PubMedThe 2H2 monoclonal antibody recognizes the precursor peptide on the immature dengue virus and might, therefore, be a useful tool for investigating the conformational change that occurs when the immature virus enters an acidic environment. During dengue virus maturation, the spiky, immature, non-infectious virions change their structure to smooth-surfaced particles in the slightly acid environment of the trans-Golgi network, thereby allowing cellular furin to cleave the precursor-membrane proteins. The dengue virions become fully infectious when they release the cleaved precursor peptide on reaching the neutral pH environment of the extracellular space. Here we report on the cryo-electron microscopy structures of the immature virus complexed with the 2H2 antigen binding fragments (Fab) at different concentrations and varied pH conditions. At neutral pH and high concentration of the Fab molecules, three Fab molecules bind to three precursor-membrane proteins on each spike of the immature virus. However, at a low concentration of the Fab molecules and at pH 7.0, only two Fab molecules bind to each spike. Changing to slightly acidic pH caused no detectable change of structure for the high Fab concentration sample, but caused severe structural damage to the low concentration sample. Therefore, the 2H2 Fab inhibits the maturation process of immature dengue virus when the Fab molecules are at high concentration, because the three Fab molecules on each spike hold the precursor-membrane molecules together, thereby inhibiting the normal conformational change that occurs during maturation. Obstruction of Dengue Virus Maturation by Fab Fragments of the 2H2 Antibody.,Wang Z, Li L, Pennington JG, Sheng J, Yap ML, Plevka P, Meng G, Sun L, Jiang W, Rossmann MG J Virol. 2013 Jun 5. PMID:23740974[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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