Summary information and primary citation
- PDB-id
- 7u5c; SNAP-derived features in text and JSON formats;
DNAproDB
- Class
- DNA binding protein-DNA
- Method
- cryo-EM (4.6 Å)
- Summary
- cryo-EM structure of human cst bound to DNA polymerase alpha-primase in a recruitment state
- Reference
- Cai SW, Zinder JC, Svetlov V, Bush MW, Nudler E, Walz T, de Lange T (2022): "Cryo-EM structure of the human CST-Pol alpha /primase complex in a recruitment state." Nat.Struct.Mol.Biol., 29, 813-819. doi: 10.1038/s41594-022-00766-y.
- Abstract
- The CST-Polα/primase complex is essential for telomere maintenance and functions to counteract resection at double-strand breaks. We report a 4.6-Å resolution cryo-EM structure of human CST-Polα/primase, captured prior to catalysis in a recruitment state stabilized by chemical cross-linking. Our structure reveals an evolutionarily conserved interaction between the C-terminal domain of the catalytic POLA1 subunit and an N-terminal expansion in metazoan CTC1. Cross-linking mass spectrometry and negative-stain EM analysis provide insight into CST binding by the flexible POLA1 N-terminus. Finally, Coats plus syndrome disease mutations previously characterized to disrupt formation of the CST-Polα/primase complex map to protein-protein interfaces observed in the recruitment state. Together, our results shed light on the architecture and stoichiometry of the metazoan fill-in machinery.
