Paf1 and Ctr9 subcomplex formation is essential for Paf1 complex assembly and functional regulation.

Area of Science:

• Molecular Biology
• Structural Biology
• Genetics

Background:

• The polymerase-associated factor 1 (Paf1) complex (Paf1C) is an evolutionarily conserved multiprotein complex.
• Paf1C plays critical roles in gene regulation, development, and is implicated in human diseases.

Purpose of the Study:

• To elucidate the structural basis of the Ctr9/Paf1 subcomplex within the Paf1C.
• To understand the assembly mechanism and functional significance of the Paf1C.

Main Methods:

• X-ray crystallography was used to determine the structures of human and yeast Ctr9/Paf1 subcomplexes.
• Investigated the role of Ctr9/Paf1 heterodimer formation in yeast viability and Paf1C assembly in vivo.

Main Results:

• Two distinct structures of human and yeast Ctr9/Paf1 heterodimers were resolved, showing conserved conformations.
• An interface between the Ctr9 tetratricopeptide repeat module and Paf1 was identified.
• Formation of the Ctr9/Paf1 heterodimer is essential for yeast Paf1C assembly and viability.
• Disruption of the Paf1-Ctr9 interaction impacts histone H3 methylation levels.

Conclusions:

• The determined structures provide mechanistic insights into Paf1C assembly and regulation.
• Structural information may explain disease-associated mutations in human PAF1 and CTR9.
• The Ctr9/Paf1 heterodimer is a fundamental unit for Paf1C formation and function.