7U5C

Cryo-EM structure of human CST bound to DNA polymerase alpha-primase in a recruitment state

Summary for 7U5C

• Entry DOI: 10.2210/pdb7u5c/pdb
• EMDB information: 26346
• Descriptor: DNA primase small subunit, IRON/SULFUR CLUSTER, DNA primase large subunit, ... (10 entities in total)
• Functional Keywords: fill-in, telomere, replication, dna binding protein, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 502115.02

Authors

Cai, S.W.,Zinder, J.C.,Svetlov, V.,Bush, M.W.,Nudler, E.,Walz, T.,de Lange, T. (deposition date: 2022-03-02, release date: 2022-05-18, Last modification date: 2024-02-14)

Primary citation

Cai, S.W.,Zinder, J.C.,Svetlov, V.,Bush, M.W.,Nudler, E.,Walz, T.,de Lange, T.
Cryo-EM structure of the human CST-Pol alpha /primase complex in a recruitment state.
Nat.Struct.Mol.Biol., 29:813-819, 2022

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-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.

PubMed: 35578024
DOI: 10.1038/s41594-022-00766-y

Experimental method

ELECTRON MICROSCOPY (4.6 Å)