Although flaviviruses co-opt the function of the host endoplasmic reticulum (ER) membrane protein complex (EMC) during infection, a mechanistic explanation for this observation remains unclear. Here, we show that the EMC promotes biogenesis of dengue virus (DENV) and Zika virus (ZIKV) non-structural multi-pass transmembrane proteins NS4A and NS4B, which are necessary for viral replication. The EMC binds to NS4B and colocalizes with the DENV replication organelle. Mapping analysis reveals that the two N-terminal marginally hydrophobic domains of NS4B confer EMC dependency. Furthermore, altering the hydrophobicity of these two marginally hydrophobic domains relieves NS4B's EMC dependency. We demonstrate that NS4B biogenesis, but not its stability, is reduced in EMC-depleted cells. Our data suggest that the EMC acts as a multi-pass transmembrane chaperone required for expression of at least two virally encoded proteins essential for flavivirus infection and point to a shared vulnerability during the viral life cycle that could be exploited for antiviral therapy.
Pubmed ID: 31067454 RIS Download
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Privately held company that develops and produces antibodies, ELISA kits, ChIP kits, proteomic kits, and other related reagents used to study cell signaling pathways that impact human health.
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View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on May 5,2022.Tool that predicts interactions between transcription factors and their regulated genes from binding motifs. Understanding vertebrate development requires unraveling the cis-regulatory architecture of gene regulation. PRISM provides accurate genome-wide computational predictions of transcription factor binding sites for the human and mouse genomes, and integrates the predictions with GREAT to provide functional biological context. Together, accurate computational binding site prediction and GREAT produce for each transcription factor: 1. putative binding sites, 2. putative target genes, 3. putative biological roles of the transcription factor, and 4. putative cis-regulatory elements through which the factor regulates each target in each functional role.
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View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
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View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
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View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
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View all literature mentionsThis polyclonal targets Zika virus NS4B protein
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets HA-probe (12CA5)
View all literature mentionsThis monoclonal targets HA-Tag
View all literature mentionsThis monoclonal targets GFP
View all literature mentionsCell line D1-4G2-4-15 is a Hybridoma with a species of origin Mus musculus (Mouse)
View all literature mentionsThis unknown targets TMEM93 (transmembrane protein 93) (against the N terminal of TMEM93) (50ug)
View all literature mentionsThis monoclonal targets TTC35 (D-7)
View all literature mentionsThis monoclonal targets K0090 (C-term)
View all literature mentionsThis polyclonal targets NS4A (Dengue virus 2) antibody
View all literature mentionsThis unknown targets EMC4
View all literature mentionsThis monoclonal targets TMEM111 (A-12)
View all literature mentionsThis polyclonal targets Dengue virus NS4B protein
View all literature mentionsThis polyclonal targets Dengue virus NS2B protein
View all literature mentionsThis monoclonal targets Calnexin (AF18)
View all literature mentionsThis monoclonal targets beta-Actin
View all literature mentionsThis monoclonal targets BAP31
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