Plasmodium falciparum CENH3 is able to functionally complement Cse4p and its, C-terminus is essential for centromere...

Area of Science:

• Molecular Biology
• Genetics
• Cell Biology

Background:

• The centromeric histone variant PfCENH3 in Plasmodium falciparum is crucial for centromere function.
• Its precise structure-function relationship and role in chromosome segregation remain largely uncharacterized.

Purpose of the Study:

• To elucidate the structural determinants of PfCENH3 and its role in centromere function.
• To identify key regions and residues essential for PfCENH3's targeting and function.

Main Methods:

• Functional complementation assays were employed to test the essentiality of PfCENH3 regions.
• Identification and association studies were performed for PfCENP-C, an inner kinetochore component.

Main Results:

• The C-terminus, specifically the CATD region within the Histone Fold Domain (HFD) of PfCENH3, is essential for centromere function.
• Specific LLAL residues within the CATD region are critical for centromere targeting and chromosome segregation.
• Plasmodium falciparum Histone H3 could not complement the yeast homologue Cse4p.
• PfCENP-C, an inner kinetochore protein, was identified and its association with PfCENH3 confirmed.

Conclusions:

• The CATD region and specific LLAL residues of PfCENH3 are key structural determinants for its function in centromere targeting and chromosome segregation.
• These findings provide critical insights into the molecular mechanisms of centromere function in Plasmodium falciparum.