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<p>The oocyst, the sporogonic stage of the malaria parasite located on the mosquito gut, is protected by a capsule, or cyst wall, which surrounds the plasma membrane. The capsule opens to release the infectious sporozoites. Previously, we identified two <Emphasis Type="Underline">O</Emphasis>ocyst <Emphasis Type="Underline">R</Emphasis>upture <Emphasis Type="Underline">P</Emphasis>roteins (ORP1-2) that are essential for capsule excystation and sporozoite egress. Both ORPs contain a Histone-Fold Domain similar to the NF-YB and -YC subunits of the trimeric human transcription factor NF-Y. Here we identify a <i>Plasmodium</i> protein, named ORP3, as a third subunit of the ORP complex. Although ORP3 is largely unrelated to the NF-YA subunit responsible for trimerization with DNA-binding specificity of NF-Y, it retains the well conserved NF-YA helix A1, responsible for trimerization with the NF-YB/C dimer. A detailed phenotypic analysis of an <i>orp3(-)</i> mutant showed a defect in oocyst opening, as observed for the for <i>orp1(-)</i> and <i>orp2(-)</i> mutants. ORP3 localizes to the periphery of the oocyst, consistent with its position at the capsule. The functional importance of the conserved helix A1 of ORP3 was confirmed, as deletion of this helix abolishes oocyst excystation. The formation of a trimeric complex between a construct containing the helix A1 with the ORP1/2 dimer was further confirmed in vitro using a Yeast-3-hybrid approach. Finally, we confirmed the motility of <i>orp(-)</i> sporozoites, suggesting that the block in parasite transmission following injection into naïve mouse is likely due to a failure in developing into exoerythrocytic forms. Our data strengthen the hypothesis that <i>Plasmodium</i> has re-purposed the NF-Y complex fold and assembly for the unique biological function of promoting oocyst excystation and sporozoite release.</p>

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Sporozoite egress from Plasmodium oocysts requires a trimeric NF-Y–like complex

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月27日

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  • Claude Marie François Preira,
  • Elena Deligianni,
  • Maria Andreadaki,
  • Sofia Tzagkaraki,
  • Emmanouil Kokkas,
  • Aneta Kołakowska,
  • Renate Gessmann,
  • Chiara Bertaso,
  • Simona Masiero,
  • Rosaria Russo,
  • Marco Nardini,
  • Inga Siden-Kiamos,
  • Louise J. Gourlay,
  • Chiara Currà

摘要

The oocyst, the sporogonic stage of the malaria parasite located on the mosquito gut, is protected by a capsule, or cyst wall, which surrounds the plasma membrane. The capsule opens to release the infectious sporozoites. Previously, we identified two Oocyst Rupture Proteins (ORP1-2) that are essential for capsule excystation and sporozoite egress. Both ORPs contain a Histone-Fold Domain similar to the NF-YB and -YC subunits of the trimeric human transcription factor NF-Y. Here we identify a Plasmodium protein, named ORP3, as a third subunit of the ORP complex. Although ORP3 is largely unrelated to the NF-YA subunit responsible for trimerization with DNA-binding specificity of NF-Y, it retains the well conserved NF-YA helix A1, responsible for trimerization with the NF-YB/C dimer. A detailed phenotypic analysis of an orp3(-) mutant showed a defect in oocyst opening, as observed for the for orp1(-) and orp2(-) mutants. ORP3 localizes to the periphery of the oocyst, consistent with its position at the capsule. The functional importance of the conserved helix A1 of ORP3 was confirmed, as deletion of this helix abolishes oocyst excystation. The formation of a trimeric complex between a construct containing the helix A1 with the ORP1/2 dimer was further confirmed in vitro using a Yeast-3-hybrid approach. Finally, we confirmed the motility of orp(-) sporozoites, suggesting that the block in parasite transmission following injection into naïve mouse is likely due to a failure in developing into exoerythrocytic forms. Our data strengthen the hypothesis that Plasmodium has re-purposed the NF-Y complex fold and assembly for the unique biological function of promoting oocyst excystation and sporozoite release.