Functionality of redox-active crysteines is required for restriction of retroviral replication by SAMHD1

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dc.contributor.authorWang, Zhonghua
dc.contributor.authorBhattacharya, Akash
dc.contributor.authorWhite, Tommy
dc.contributor.authorBuffone, Cindy
dc.contributor.authorMcCabe, Aine
dc.contributor.authorNguyen, Laura A.
dc.contributor.authorShepard, Caitlin N.
dc.contributor.authorPardo, Sammy
dc.contributor.authorKim, Baek
dc.contributor.authorWeintraub, Susan T.
dc.contributor.authorDemeler, Borries
dc.contributor.authorDiaz-Griffero, Felipe
dc.contributor.authorIvanov, Dmitri N.
dc.date.accessioned2021-07-05T21:57:57Z
dc.date.available2021-07-05T21:57:57Z
dc.date.issued2018
dc.descriptionOpen access article. Creative Commons 4.0 International License (CC BY 4.0) appliesen_US
dc.description.abstractSAMHD1 is a dNTP triphosphohydrolase (dNTPase)that impairs retroviral replication in a subset of non-cycling immune cells. Here we show that SAMHD1is a redox-sensitive enzyme and identify threeredox-active cysteines within the protein: C341,C350, and C522. The three cysteines reside nearone another and the allosteric nucleotide bindingsite. Mutations C341S and C522S abolish the abilityof SAMHD1 to restrict HIV replication, whereas theC350S mutant remains restriction competent. TheC522S mutation makes the protein resistant to inhibi-tion by hydrogen peroxide but has no effect onthe tetramerization-dependent dNTPase activity ofSAMHD1in vitroor on the ability of SAMHD1 todeplete cellular dNTPs. Our results reveal that enzy-matic activation of SAMHD1 via nucleotide-depen-dent tetramerization is not sufficient for the estab-lishment of the antiviral state and that retroviralrestriction depends on the ability of the protein to un-dergo redox transformations.en_US
dc.description.peer-reviewYesen_US
dc.identifier.citationWang, Z., Bhattacharya, A., White, T., Buffone, C., McCabe, A., Nguyen, L. A., Shepard, C. N., Pardo, S., Kim, B., Weintraub, S. T., Demeler, B., Diaz-Griffero, F., & Ivanov, D. N. (2018). Functionality of redox-active crysteines is required for restriction of retroviral replication by SAMHD1. Cell Reports, 24(4), 815-823. https://doi.org/10.1016/j.celrep.2018.06.090en_US
dc.identifier.urihttps://hdl.handle.net/10133/5941
dc.language.isoen_USen_US
dc.publisherCell Pressen_US
dc.publisher.departmentDepartment of Chemistry and Biochemistryen_US
dc.publisher.facultyArts and Scienceen_US
dc.publisher.institutionUniversity of Texas Health Science Centeren_US
dc.publisher.institutionAlbert Einstein College of Medicineen_US
dc.publisher.institutionEmory School of Medicineen_US
dc.publisher.institutionKyunghee Universityen_US
dc.publisher.institutionUniversity of Lethbridgeen_US
dc.publisher.urlhttps://doi.org/10.1016/j.celrep.2018.06.090en_US
dc.subjectSAMHD1en_US
dc.subjectHIVen_US
dc.subjectInnate immunityen_US
dc.subjectRestriction factorsen_US
dc.subjectdNTPen_US
dc.subjectRedox signalingen_US
dc.subjectReactive oxygen speciesen_US
dc.subject.lcshRetroviruses
dc.subject.lcshNatural immunity
dc.subject.lcshActive oxygen
dc.titleFunctionality of redox-active crysteines is required for restriction of retroviral replication by SAMHD1en_US
dc.typeArticleen_US
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