TY - JOUR
T1 - Crystal Structure of the Core Module of the Yeast Paf1 Complex
AU - Chen, Feilong
AU - Liu, Beibei
AU - Zeng, Jianwei
AU - Guo, Lu
AU - Ge, Xuan
AU - Feng, Wei
AU - Li, De Feng
AU - Zhou, Hao
AU - Long, Jiafu
N1 - Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2022/1/30
Y1 - 2022/1/30
N2 - The highly conserved multifunctional polymerase-associated factor 1 (Paf1) complex (PAF1C), which consists of five core subunits: Ctr9, Paf1, Leo1, Cdc73, and Rtf1, acts as a diverse hub that regulates all stages of RNA polymerase II-mediated transcription and various other cellular functions. However, the underlying mechanisms remain unclear. Here, we report the crystal structure of the core module derived from a quaternary Ctr9/Paf1/Cdc73/Rtf1 complex of S. cerevisiae PAF1C, which reveals interfaces between the tetratricopeptide repeat module in Ctr9 and Cdc73 or Rtf1, and find that the Ctr9/Paf1 subcomplex is the key scaffold for PAF1C assembly. Our study demonstrates that Cdc73 binds Ctr9/Paf1 subcomplex with a very similar conformation within thermophilic fungi or human PAF1C, and that the binding of Cdc73 to PAF1C is important for yeast growth. Importantly, our structure reveals for the first time that the extreme C-terminus of Rtf1 adopts an “L”-shaped structure, which interacts with Ctr9 specifically. In addition, disruption of the binding of either Cdc73 or Rtf1 to PAF1C greatly affects the normal level of histone H2B K123 monoubiquitination in vivo. Collectively, our results provide a structural insight into the architecture of the quaternary Ctr9/Paf1/Cdc73/Rtf1 complex and PAF1C functional regulation.
AB - The highly conserved multifunctional polymerase-associated factor 1 (Paf1) complex (PAF1C), which consists of five core subunits: Ctr9, Paf1, Leo1, Cdc73, and Rtf1, acts as a diverse hub that regulates all stages of RNA polymerase II-mediated transcription and various other cellular functions. However, the underlying mechanisms remain unclear. Here, we report the crystal structure of the core module derived from a quaternary Ctr9/Paf1/Cdc73/Rtf1 complex of S. cerevisiae PAF1C, which reveals interfaces between the tetratricopeptide repeat module in Ctr9 and Cdc73 or Rtf1, and find that the Ctr9/Paf1 subcomplex is the key scaffold for PAF1C assembly. Our study demonstrates that Cdc73 binds Ctr9/Paf1 subcomplex with a very similar conformation within thermophilic fungi or human PAF1C, and that the binding of Cdc73 to PAF1C is important for yeast growth. Importantly, our structure reveals for the first time that the extreme C-terminus of Rtf1 adopts an “L”-shaped structure, which interacts with Ctr9 specifically. In addition, disruption of the binding of either Cdc73 or Rtf1 to PAF1C greatly affects the normal level of histone H2B K123 monoubiquitination in vivo. Collectively, our results provide a structural insight into the architecture of the quaternary Ctr9/Paf1/Cdc73/Rtf1 complex and PAF1C functional regulation.
KW - Heterotetramer
KW - histone H2B K123 monoubiquitination
KW - Paf1 complex
KW - tetratricopeptide repeat (TPR)
KW - Transcription
UR - http://www.scopus.com/inward/record.url?scp=85120415002&partnerID=8YFLogxK
U2 - 10.1016/j.jmb.2021.167369
DO - 10.1016/j.jmb.2021.167369
M3 - Article
C2 - 34852272
AN - SCOPUS:85120415002
SN - 0022-2836
VL - 434
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 2
M1 - 167369
ER -