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<p>Sexual commitment in Plasmodium parasites is essential for malaria transmission, yet the signaling events initiating sexual conversion in only a subpopulation of parasites remain unclear. We discovered a single valine(V<sub>2163</sub>) to leucine(L<sub>2163</sub>) mutation in a transcription factor required for <i>P. falciparum</i> gametocytogenesis (AP2-G) that abrogates sexual differentiation. AP2-G.L<sub>2163</sub> does not bind the <i>ap2-g</i> consensus motif, GnGTAC, or stimulate gene transcription, including autoregulation. The GDV1-dependent expression of AP2-G.L<sub>2163</sub> demonstrates GDV1’s critical role in the initial activation of the silent <i>ap2-g</i> locus in the absence of functional AP2-G. While AP2-G.V<sub>2163</sub> is required for MSRP1 expression, providing a marker that discriminates early from late sexually committed schizonts. Together this work demonstrates that V<sub>2163</sub> in AP2-G plays a critical role in DNA binding, highlighting the functional importance of this specific region for malaria transmission as well as the key role of GDV1 in the initial activation of <i>ap2-g</i> expression and induction of sexual differentiation.</p>

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A single valine to leucine switch disrupts Plasmodium falciparum AP2-G DNA binding and reveals GDV1’s role in ap2-g activation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月17日

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  • Surendra K. Prajapati,
  • Jeffrey X. Dong,
  • Belinda J. Morahan,
  • Thoai Dotrang,
  • Michelle C. Barbeau,
  • April E. Williams,
  • Daniel Hupalo,
  • Matthew D. Wilkerson,
  • Clifton L. Dalgard,
  • Bjorn F. C. Kafsack,
  • Manuel Llinás,
  • Kim C. Williamson

摘要

Sexual commitment in Plasmodium parasites is essential for malaria transmission, yet the signaling events initiating sexual conversion in only a subpopulation of parasites remain unclear. We discovered a single valine(V2163) to leucine(L2163) mutation in a transcription factor required for P. falciparum gametocytogenesis (AP2-G) that abrogates sexual differentiation. AP2-G.L2163 does not bind the ap2-g consensus motif, GnGTAC, or stimulate gene transcription, including autoregulation. The GDV1-dependent expression of AP2-G.L2163 demonstrates GDV1’s critical role in the initial activation of the silent ap2-g locus in the absence of functional AP2-G. While AP2-G.V2163 is required for MSRP1 expression, providing a marker that discriminates early from late sexually committed schizonts. Together this work demonstrates that V2163 in AP2-G plays a critical role in DNA binding, highlighting the functional importance of this specific region for malaria transmission as well as the key role of GDV1 in the initial activation of ap2-g expression and induction of sexual differentiation.