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<p><?tk 2?>σ<sup>B</sup>, a <i>Staphylococcus aureus</i>-encoded alternative sigma factor, is inhibited by RsbW, an anti-sigma factor. RsbW also dimerizes in solution and phosphorylates RsbV, an RsbW antagonist. Of the predicted RsbW residues involved in its dimerization and/or binding cognate factors, the roles of Arg 11, Arg 32, and Lys 44 have been demonstrated here using various tools. The structural models of three RsbW mutants, harboring Ala at positions 11, 32, and 44, were built up, and their analyses suggested that all of the above Lys/Arg residues may be involved in the dimerization of this protein. Similar analyses indicated that Lys 44 and Arg 32 may be needed for binding σ<sup>B3</sup>, the domain 3 of σ<sup>B</sup>. The docking studies have confirmed the roles of Arg 11 and Arg 32 in the dimerization of RsbW, and revealed that its association with σ<sup>B3</sup> requires Arg 32 and Lys 44. Additionally, the simulation studies proposed that all of the above Lys/Arg may be needed for its structure maintenance. To verify the computational data, three Ala-substituted RsbW mutants were also purified, and their characterization indicates that the change of Arg 11 or Lys 44 to Ala, compared to the change of Arg 32 to Ala, impacts the structure, RsbV/ σ<sup>B3</sup> binding affinity, and phosphorylation activity of RsbW more severely. Further, the dimerization ability of RsbW was partly affected by Ala substitution at positions 11 and 32. Jointly, Arg 11, Arg 32, and Lys 44 of RsbW are crucial residues for this σ<sup>B</sup> inhibitor and kinase. Knowledge of crucial RsbW residues may be useful for designing antistaphylococcal drugs in the future.</p>

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Arginine 11, Arginine 32, and Lysine 44 of a Staphylococcal Anti-sigma Factor are Indispensable Residues

  • 期刊论文

  • 发表日期：

    2025年11月12日

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  • Debasmita Sinha,
  • Debabrata Sinha,
  • Tushar Chakraborty,
  • Subrata Sau

摘要

σB, a Staphylococcus aureus-encoded alternative sigma factor, is inhibited by RsbW, an anti-sigma factor. RsbW also dimerizes in solution and phosphorylates RsbV, an RsbW antagonist. Of the predicted RsbW residues involved in its dimerization and/or binding cognate factors, the roles of Arg 11, Arg 32, and Lys 44 have been demonstrated here using various tools. The structural models of three RsbW mutants, harboring Ala at positions 11, 32, and 44, were built up, and their analyses suggested that all of the above Lys/Arg residues may be involved in the dimerization of this protein. Similar analyses indicated that Lys 44 and Arg 32 may be needed for binding σB3, the domain 3 of σB. The docking studies have confirmed the roles of Arg 11 and Arg 32 in the dimerization of RsbW, and revealed that its association with σB3 requires Arg 32 and Lys 44. Additionally, the simulation studies proposed that all of the above Lys/Arg may be needed for its structure maintenance. To verify the computational data, three Ala-substituted RsbW mutants were also purified, and their characterization indicates that the change of Arg 11 or Lys 44 to Ala, compared to the change of Arg 32 to Ala, impacts the structure, RsbV/ σB3 binding affinity, and phosphorylation activity of RsbW more severely. Further, the dimerization ability of RsbW was partly affected by Ala substitution at positions 11 and 32. Jointly, Arg 11, Arg 32, and Lys 44 of RsbW are crucial residues for this σB inhibitor and kinase. Knowledge of crucial RsbW residues may be useful for designing antistaphylococcal drugs in the future.