Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structural mechanism of TOPBP1 activating the ATR-ATRIP replication checkpoint kinase.
Journal, issue, pages	Nat Struct Mol Biol, Year 2026
Publish date	Jul 23, 2026
Authors	Buren Li / Ayat Yaseen / Nikola P Pavletich /
PubMed Abstract	The ATR protein kinase preserves genomic integrity during DNA replication by controlling checkpoints needed for the orderly progression of S phase and for the responses to replication stress. ATR, ...The ATR protein kinase preserves genomic integrity during DNA replication by controlling checkpoints needed for the orderly progression of S phase and for the responses to replication stress. ATR, with its obligate partner ATRIP, is activated by the TOPBP1 and ETAA1 proteins, which control different branches of ATR signaling. TOPBP1 is essential for induction of the S phase checkpoint in response to stalled replication forks, while ETAA1 is required for timely progression to mitosis from an unperturbed S phase. TOPBP1 and ETAA1 contain ATR-activating domains (AADs) of limited homology, but how they activate ATR has not yet been fully elucidated. Here we present the 3.0-Å cryo-EM structure of the human ATR-ATRIP complex bound to the TOPBP1 AAD, showing that TOPBP1 activates ATR by inducing a global conformational change that allosterically realigns active site residues in the kinase domain ~70 Å away. We also present the 3.3-Å structure of the ATR-ATRIP-ETAA1 AAD complex, which reveals a binding mode distinct from TOPBP1. Our data suggest that the distinct binding modes of TOPBP1 and ETAA1 contribute to the different cellular contexts and outcomes of ATR-ATRIP activation.
External links	Nat Struct Mol Biol / PubMed:42493622
Methods	EM (single particle)
Resolution	2.4 - 3.5 Å
Structure data	EMDB-74000: Consensus reconstruction of symmetric class of ATR-ATRIP-ETAA1 AAD Method: EM (single particle) / Resolution: 3.3 Å EMDB-74001: Reconstruction focused at N-heat-ATRIP of symmetric class of ATR-ATRIP-ETAA1 AAD Method: EM (single particle) / Resolution: 3.5 Å EMDB-74002: Reconstruction focused at N-heat-M-heat-FAT of symmetric class of ATR-ATRIP-ETAA1 AAD Method: EM (single particle) / Resolution: 3.3 Å EMDB-74003: Reconstruction focused at FAT-kinase of symmetric class of ATR-ATRIP-ETAA1 AAD Method: EM (single particle) / Resolution: 3.1 Å EMDB-74004: Consensus reconstruction of apo-ATR-ATRIP Method: EM (single particle) / Resolution: 2.5 Å EMDB-74005: Reconstruction focused at N-heat-ATRIP of apo-ATR-ATRIP Method: EM (single particle) / Resolution: 3.1 Å EMDB-74006: Reconstruction focused at N-heat-ATRIP-M-heat-FAT of closed protomer of apo-ATR-ATRIP Method: EM (single particle) / Resolution: 3.2 Å EMDB-74007: Reconstruction focused at N-heat-ATRIP-M-heat-FAT of open protomer of apo-ATR-ATRIP Method: EM (single particle) / Resolution: 3.3 Å EMDB-74010: Reconstruction focused at FAT-kinase of apo-ATR-ATRIP Method: EM (single particle) / Resolution: 2.4 Å EMDB-74012: Consensus reconstruction of ATR-ATRIP-TOPBP1 AAD Method: EM (single particle) / Resolution: 3.2 Å EMDB-74013: Consensus reconstruction of ATR-ATRIP-TOPBP1 AAD (monomer after symmetry expansion and signal subtraction) Method: EM (single particle) / Resolution: 3.2 Å EMDB-74014: Reconstruction focused at N-heat-ATRIP of ATR-ATRIP-TOPBP1 AAD monomer Method: EM (single particle) / Resolution: 3.0 Å EMDB-74015: Reconstruction focused at N-heat-ATRIP-M-heat-FAT of ATR-ATRIP-TOPBP1 AAD monomer Method: EM (single particle) / Resolution: 3.0 Å EMDB-74016: Reconstruction focused at FAT-kinase of ATR-ATRIP-TOPBP1 AAD monomer Method: EM (single particle) / Resolution: 3.0 Å 74045 9zcy EMDB-74045, PDB-9zcy: Cryo-EM structure of apo-ATR-ATRIP Method: EM (single particle) / Resolution: 2.5 Å 74048 9zd1 EMDB-74048, PDB-9zd1: Cryo-EM structure of ATR-ATRIP-TOPBP1 AAD Method: EM (single particle) / Resolution: 3.2 Å 74050 9zd3 EMDB-74050, PDB-9zd3: Cryo-EM structure of ATR-ATRIP-ETAA1 AAD Method: EM (single particle) / Resolution: 3.0 Å 74051 9zd4 EMDB-74051, PDB-9zd4: Cryo-EM structure of symmetric class of ATR-ATRIP-ETAA1 AAD Method: EM (single particle) / Resolution: 3.3 Å EMDB-76984: Consensus reconstruction of ATR-ATRIP-ETAA1 AAD(S95D/S111D) Method: EM (single particle) / Resolution: 2.9 Å EMDB-76986: Reconstruction focused at N-heat-ATRIP of ATR-ATRIP-ETAA1 AAD (S95D/S111D) Method: EM (single particle) / Resolution: 2.9 Å EMDB-76987: Reconstruction focused at N-heat-ATRIP-M-heat-FAT of closed protomer of ATR-ATRIP-ETAA1 AAD (S95D/S111D) Method: EM (single particle) / Resolution: 3.1 Å EMDB-76988: Reconstruction focused at N-heat-ATRIP-M-heat of open protomer of ATR-ATRIP-ETAA1 AAD (S95D/S111D) Method: EM (single particle) / Resolution: 3.2 Å EMDB-76989: Reconstruction focused at FAT-kinase of ATR-ATRIP-ETAA1 AAD (S95D/S111D) Method: EM (single particle) / Resolution: 2.7 Å 76990 13de EMDB-76990, PDB-13de: Cryo-EM structure of ATR-ATRIP-ETAA1 AAD (S95D/S111D) Method: EM (single particle) / Resolution: 2.9 Å
Chemicals	ChemComp-ZN: Unknown entry ChemComp-MG: Unknown entry ChemComp-ANP: PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / AMP-PNP, energy-carrying molecule analogue*YM
Source	homo sapiens (human)
Keywords	NUCLEAR PROTEIN / kinase / PI3K-related kinase / complex / activator / replication stress response / replication checkpoint