EMD-26346
Cryo-EM structure of human CST bound to DNA polymerase alpha-primase in a recruitment state
EMD-26346
Single-particle4.6 Å
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Map released: 18/05/2022
Last modified: 14/02/2024
Sample Organism:
Homo sapiens
Sample: Human CST bound to DNA polymerase alpha(POLA1 delta N)-primase in a recruitment state
Fitted models: 7u5c (Avg. Q-score: 0.33)
Raw data: EMPIAR-11131
Deposition Authors: Cai SW
,
Zinder JC
,
Svetlov V
,
Bush MW,
Nudler E
,
Walz T
,
de Lange T
Sample: Human CST bound to DNA polymerase alpha(POLA1 delta N)-primase in a recruitment state
Fitted models: 7u5c (Avg. Q-score: 0.33)
Raw data: EMPIAR-11131
Deposition Authors: Cai SW
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Cryo-EM structure of the human CST-Pol alpha /primase complex in a recruitment state.
Cai SW
,
Zinder JC
,
Svetlov V
,
Bush MW,
Nudler E
,
Walz T
,
de Lange T
(2022) Nat Struct Mol Biol , 29 , 813 - 819
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(2022) Nat Struct Mol Biol , 29 , 813 - 819
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.
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.