10779/crick.12652334.v1
William CH Chao
William CH
Chao
Yasuto Murayama
Yasuto
Murayama
Sofía Muñoz
Sofía
Muñoz
Alessandro Costa
Alessandro
Costa
Frank Uhlmann
Frank
Uhlmann
Martin R Singleton
Martin R
Singleton
Structural studies reveal the functional modularity of the Scc2-Scc4 cohesin loader
The Francis Crick Institute
2020
Ascomycota
Chromosomal Proteins, Non-Histone
Fungal Proteins
Protein Structure, Quaternary
Protein Structure, Secondary
Protein Structure, Tertiary
Costa
Uhlmann
Singleton
SB-ack
EM-ack
PRT-ack
0601 Biochemistry and Cell Biology
2020-07-14 12:54:02
Journal contribution
https://crick.figshare.com/articles/journal_contribution/Structural_studies_reveal_the_functional_modularity_of_the_Scc2-Scc4_cohesin_loader/12652334
The remarkable accuracy of eukaryotic cell division is partly maintained by the cohesin complex acting as a molecular glue to prevent premature sister chromatid separation. The loading of cohesin onto chromosomes is catalyzed by the Scc2-Scc4 loader complex. Here, we report the crystal structure of Scc4 bound to the N terminus of Scc2 and show that Scc4 is a tetratricopeptide repeat (TPR) superhelix. The Scc2 N terminus adopts an extended conformation and is entrapped by the core of the Scc4 superhelix. Electron microscopy (EM) analysis reveals that the Scc2-Scc4 loader complex comprises three domains: a head, body, and hook. Deletion studies unambiguously assign the Scc2N-Scc4 as the globular head domain, whereas in vitro cohesin loading assays show that the central body and the hook domains are sufficient to catalyze cohesin loading onto circular DNA, but not chromatinized DNA in vivo, suggesting a possible role for Scc4 as a chromatin adaptor.