5NP0

Closed dimer of human ATM (Ataxia telangiectasia mutated)

Summary for 5NP0

• Entry DOI: 10.2210/pdb5np0/pdb
• EMDB information: 3669
• Descriptor: Serine-protein kinase ATM (1 entity in total)
• Functional Keywords: pikk, kinase, dna-repair, heat-repeats, signaling protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 704787.94

Authors

Baretic, D.,Pollard, H.K.,Fisher, D.I.,Johnson, C.M.,Santhanam, B.,Truman, C.M.,Kouba, T.,Fersht, A.R.,Phillips, C.,Williams, R.L. (deposition date: 2017-04-13, release date: 2017-05-17, Last modification date: 2024-05-15)

Primary citation

Baretic, D.,Pollard, H.K.,Fisher, D.I.,Johnson, C.M.,Santhanam, B.,Truman, C.M.,Kouba, T.,Fersht, A.R.,Phillips, C.,Williams, R.L.
Structures of closed and open conformations of dimeric human ATM.
Sci Adv, 3:e1700933-e1700933, 2017

PubMed Abstract: ATM (ataxia-telangiectasia mutated) is a phosphatidylinositol 3-kinase-related protein kinase (PIKK) best known for its role in DNA damage response. ATM also functions in oxidative stress response, insulin signaling, and neurogenesis. Our electron cryomicroscopy (cryo-EM) suggests that human ATM is in a dynamic equilibrium between closed and open dimers. In the closed state, the PIKK regulatory domain blocks the peptide substrate-binding site, suggesting that this conformation may represent an inactive or basally active enzyme. The active site is held in this closed conformation by interaction with a long helical hairpin in the TRD3 (tetratricopeptide repeats domain 3) domain of the symmetry-related molecule. The open dimer has two protomers with only a limited contact interface, and it lacks the intermolecular interactions that block the peptide-binding site in the closed dimer. This suggests that the open conformation may be more active. The ATM structure shows the detailed topology of the regulator-interacting N-terminal helical solenoid. The ATM conformational dynamics shown by the structures represent an important step in understanding the enzyme regulation.

PubMed: 28508083
DOI: 10.1126/sciadv.1700933

Experimental method

ELECTRON MICROSCOPY (5.7 Å)