Scholarlink

<p>Coronaviruses rely on a multifunctional replication-transcription complex to ensure genome fidelity and support viral propagation. Within this complex, the nsp14-nsp10 heterodimer possesses 3’−5’ exoribonuclease (ExoN) activity, while nsp14 alone functions as an N7-methyltransferase and the nsp16/nsp10 complex completes viral RNA capping via its 2′-O-methyltransferase. Here, we report that nsp14 and nsp10 ligate [Fe<sub>4</sub>S<sub>4</sub>] clusters when purified anoxically, in sites previously modeled as zinc centers. Quantum mechanics/molecular mechanics simulations revealed distinct reduction potentials for these iron-sulfur (Fe-S) clusters, and redox titrations demonstrated that changes in oxidation state modulate RNA binding by nsp14 and the nsp10/nsp16 complex. Functionally, Fe-S clusters enhance the methyltransferase activities of nsp14 and nsp10/nsp16, while leaving the ExoN activity unaffected. These findings uncover a redox-regulated role for Fe-S clusters in SARS-CoV-2 RNA processing and suggest that the viral core enzymatic functions may be modulated by the redox state of their Fe-S cofactors.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Iron-sulfur clusters in SARS-CoV-2 exoribonuclease and methyltransferase complexes: relevance for viral genome proofreading and capping

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月15日

查看全文
  • Nunziata Maio,
  • Umberto Terranova,
  • Yan Li,
  • J. Martin Bollinger Jr.,
  • Carsten Krebs,
  • Tracey A. Rouault

摘要

Coronaviruses rely on a multifunctional replication-transcription complex to ensure genome fidelity and support viral propagation. Within this complex, the nsp14-nsp10 heterodimer possesses 3’−5’ exoribonuclease (ExoN) activity, while nsp14 alone functions as an N7-methyltransferase and the nsp16/nsp10 complex completes viral RNA capping via its 2′-O-methyltransferase. Here, we report that nsp14 and nsp10 ligate [Fe4S4] clusters when purified anoxically, in sites previously modeled as zinc centers. Quantum mechanics/molecular mechanics simulations revealed distinct reduction potentials for these iron-sulfur (Fe-S) clusters, and redox titrations demonstrated that changes in oxidation state modulate RNA binding by nsp14 and the nsp10/nsp16 complex. Functionally, Fe-S clusters enhance the methyltransferase activities of nsp14 and nsp10/nsp16, while leaving the ExoN activity unaffected. These findings uncover a redox-regulated role for Fe-S clusters in SARS-CoV-2 RNA processing and suggest that the viral core enzymatic functions may be modulated by the redox state of their Fe-S cofactors.