EMC1-dependent stabilization drives membrane penetration of a partially destabilized non-enveloped virus

Bagchi, Parikshit; Inoue, Takamitsu; Tsai, Billy

doi:10.7554/elife.21470

Cited by 54 publications

(62 citation statements)

References 50 publications

(112 reference statements)

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“…We previously identified novel B14- and C18-binding factors that execute distinct functions in supporting this viral membrane transport process [6,20,21]. However, potential B12-interacting proteins that may also play roles during SV40 ER membrane penetration have yet to be identified.…”

Section: Resultsmentioning

confidence: 99%

Regulated Erlin-dependent release of the B12 transmembrane J-protein promotes ER membrane penetration of a non-enveloped virus

Inoue

Tsai

2017

PLoS Pathog

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The molecular mechanism by which non-enveloped viruses penetrate biological membranes remains enigmatic. The non-enveloped polyomavirus SV40 penetrates the endoplasmic reticulum (ER) membrane to reach the cytosol and cause infection. We previously demonstrated that SV40 creates its own membrane penetration structure by mobilizing select transmembrane proteins to distinct puncta in the ER membrane called foci that likely function as the cytosol entry sites. How these ER membrane proteins reorganize into the foci is unknown. B12 is a transmembrane J-protein that mobilizes into the foci to promote cytosol entry of SV40. Here we identify two closely related ER membrane proteins Erlin1 and Erlin2 (Erlin1/2) as B12-interaction partners. Strikingly, SV40 recruits B12 to the foci by inducing release of this J-protein from Erlin1/2. Our data thus reveal how a non-enveloped virus promotes its own membrane translocation by triggering the release and recruitment of a critical transport factor to the membrane penetration site.

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Section: Resultsmentioning

confidence: 99%

Regulated Erlin-dependent release of the B12 transmembrane J-protein promotes ER membrane penetration of a non-enveloped virus

Inoue

Tsai

2017

PLoS Pathog

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“…For example, the OST complex has recently been identified to associate with proteins in the ER membrane complex (EMC), which has been reported to act as a chaperone for multipass transmembrane proteins, of which NS4B is an example (20, 21). In this model, MAGT1, through its oxidoreductase activity, might transiently interact with NS4B, recruiting it to the EMC as an NS4B chaperone.…”

Section: Discussionmentioning

confidence: 99%

Dengue Virus Hijacks a Noncanonical Oxidoreductase Function of a Cellular Oligosaccharyltransferase Complex

Lin

Cherepanova

Bozzacco

et al. 2017

mBio

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Dengue virus (DENV) is the most common arboviral infection globally, infecting an estimated 390 million people each year. We employed a genome-wide clustered regularly interspaced short palindromic repeat (CRISPR) screen to identify host dependency factors required for DENV propagation and identified the oligosaccharyltransferase (OST) complex as an essential host factor for DENV infection. Mammalian cells express two OSTs containing either STT3A or STT3B. We found that the canonical catalytic function of the OSTs as oligosaccharyltransferases is not necessary for DENV infection, as cells expressing catalytically inactive STT3A or STT3B are able to support DENV propagation. However, the OST subunit MAGT1, which associates with STT3B, is also required for DENV propagation. MAGT1 expression requires STT3B, and a catalytically inactive STT3B also rescues MAGT1 expression, supporting the hypothesis that STT3B serves to stabilize MAGT1 in the context of DENV infection. We found that the oxidoreductase CXXC active site motif of MAGT1 was necessary for DENV propagation, as cells expressing an AXXA MAGT1 mutant were unable to support DENV infection. Interestingly, cells expressing single-cysteine CXXA or AXXC mutants of MAGT1 were able to support DENV propagation. Utilizing the engineered peroxidase APEX2, we demonstrate the close proximity between MAGT1 and NS1 or NS4B during DENV infection. These results reveal that the oxidoreductase activity of the STT3B-containing OST is necessary for DENV infection, which may guide the development of antiviral agents targeting DENV.

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“…Such factors could promote folding of complex lumenal or cytoplasmic domains within EMC clients or triage misfolded forms to degradation pathways. Multiple lines of evidence implicate the EMC as a 'quality control hub' for membrane proteins, functioning as a context-dependent binding partner for both general and specialised molecular chaperones (Bagchi et al, 2016;Coelho et al, 2019;Kudze et al, 2018;Richard et al, 2013;Shurtleff et al, 2018; summarised in Fig. 2A).…”

Section: Box 2 the Emc Assists In Polytopic Membrane Protein Biogenesismentioning

confidence: 99%

Squaring the EMC – how promoting membrane protein biogenesis impacts cellular functions and organismal homeostasis

Volkmar

Christianson

2020

Journal of Cell Science

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Integral membrane proteins play key functional roles at organelles and the plasma membrane, necessitating their efficient and accurate biogenesis to ensure appropriate targeting and activity. The endoplasmic reticulum membrane protein complex (EMC) has recently emerged as an important eukaryotic complex for biogenesis of integral membrane proteins by promoting insertion and stability of atypical and sub-optimal transmembrane domains (TMDs). Although confirmed as a bona fide complex almost a decade ago, light is just now being shed on the mechanism and selectivity underlying the cellular responsibilities of the EMC. In this Review, we revisit the myriad of functions attributed the EMC through the lens of these new mechanistic insights, to address questions of the cellular and organismal roles the EMC has evolved to undertake.

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EMC1-dependent stabilization drives membrane penetration of a partially destabilized non-enveloped virus

Cited by 54 publications

References 50 publications

Regulated Erlin-dependent release of the B12 transmembrane J-protein promotes ER membrane penetration of a non-enveloped virus

Regulated Erlin-dependent release of the B12 transmembrane J-protein promotes ER membrane penetration of a non-enveloped virus

Dengue Virus Hijacks a Noncanonical Oxidoreductase Function of a Cellular Oligosaccharyltransferase Complex

Squaring the EMC – how promoting membrane protein biogenesis impacts cellular functions and organismal homeostasis

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