دورية أكاديمية
Phage T3 overcomes the BREX defense through SAM cleavage and inhibition of SAM synthesis by SAM lyase.
| العنوان: | Phage T3 overcomes the BREX defense through SAM cleavage and inhibition of SAM synthesis by SAM lyase. |
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| المؤلفون: | Andriianov A; Skolkovo Institute of Science and Technology, Moscow 143028, Russia., Trigüis S; Department of Cell and Molecular Biology, Uppsala University, BMC, Box 596, 751 24 Uppsala, Sweden., Drobiazko A; Skolkovo Institute of Science and Technology, Moscow 143028, Russia., Sierro N; Philip Morris International R&D, Philip Morris Products S.A., 2000 Neuchatel, Switzerland., Ivanov NV; Philip Morris International R&D, Philip Morris Products S.A., 2000 Neuchatel, Switzerland., Selmer M; Department of Cell and Molecular Biology, Uppsala University, BMC, Box 596, 751 24 Uppsala, Sweden. Electronic address: maria.selmer@icm.uu.se., Severinov K; Waksman Institute of Microbiology, Piscataway, NJ 08854, USA. Electronic address: severik@waksman.rutgers.edu., Isaev A; Skolkovo Institute of Science and Technology, Moscow 143028, Russia. Electronic address: artem.isaev@skoltech.ru. |
| المصدر: | Cell reports [Cell Rep] 2023 Aug 29; Vol. 42 (8), pp. 112972. Date of Electronic Publication: 2023 Aug 13. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Cambridge, MA] : Cell Press, c 2012- |
| مواضيع طبية MeSH: | Bacteriophage T3*/metabolism , Bacteriophages*/genetics, Cryoelectron Microscopy ; Escherichia coli/genetics ; S-Adenosylmethionine/metabolism |
| مستخلص: | Bacteriophage T3 encodes a SAMase that, through cleavage of S-adenosyl methionine (SAM), circumvents the SAM-dependent type I restriction-modification (R-M) defense. We show that SAMase also allows T3 to evade the BREX defense. Although SAM depletion weakly affects BREX methylation, it completely inhibits the defensive function of BREX, suggesting that SAM could be a co-factor for BREX-mediated exclusion of phage DNA, similar to its anti-defense role in type I R-M. The anti-BREX activity of T3 SAMase is mediated not just by enzymatic degradation of SAM but also by direct inhibition of MetK, the host SAM synthase. We present a 2.8 Å cryoelectron microscopy (cryo-EM) structure of the eight-subunit T3 SAMase-MetK complex. Structure-guided mutagenesis reveals that this interaction stabilizes T3 SAMase in vivo, further stimulating its anti-BREX activity. This work provides insights in the versatility of bacteriophage counterdefense mechanisms and highlights the role of SAM as a co-factor of diverse bacterial immunity systems. Competing Interests: Declaration of interests N.S. and N.V.I. are employees of Philip Morris International. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: BREX; CP: Microbiology; MetK; S-adenosyl methionine; SAM synthase; SAMase; anti-restriction; bacteriophage T3; phage defense; restriction-modification; single-particle cryo-EM |
| المشرفين على المادة: | 7LP2MPO46S (S-Adenosylmethionine) |
| تواريخ الأحداث: | Date Created: 20230814 Date Completed: 20230904 Latest Revision: 20230906 |
| رمز التحديث: | 20230906 |
| DOI: | 10.1016/j.celrep.2023.112972 |
| PMID: | 37578860 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2211-1247 |
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| DOI: | 10.1016/j.celrep.2023.112972 |