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Title | Cryo-EM structure of the human CST-Polα/primase complex in a recruitment state. |
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Journal, issue, pages | Nat Struct Mol Biol, Vol. 29, Issue 8, Page 813-819, Year 2022 |
Publish date | May 16, 2022 |
Authors | Sarah W Cai / John C Zinder / Vladimir Svetlov / Martin W Bush / Evgeny Nudler / Thomas Walz / Titia de Lange / |
PubMed 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- ...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. |
External links | Nat Struct Mol Biol / PubMed:35578024 / PubMed Central |
Methods | EM (single particle) |
Resolution | 4.6 - 16.0 Å |
Structure data | EMDB-26346, PDB-7u5c: EMDB-26347: Human CST bound to full-length DNA polymerase alpha-primase in a recruitment state |
Chemicals | ChemComp-ZN: ChemComp-SF4: |
Source |
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Keywords | DNA BINDING PROTEIN/DNA / Fill-in / Telomere / Replication / DNA BINDING PROTEIN / DNA BINDING PROTEIN-DNA complex |