6JXC

Tel1 kinase butterfly symmetric dimer

Summary for 6JXC

• Entry DOI: 10.2210/pdb6jxc/pdb
• EMDB information: 9893
• Descriptor: Serine/threonine-protein kinase TEL1 (1 entity in total)
• Functional Keywords: kinase, responds to dna double-strand breaks, transferase
• Biological source: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
• Total number of polymer chains: 1
• Total formula weight: 321888.31

Authors

Xin, J. (deposition date: 2019-04-23, release date: 2019-07-03, Last modification date: 2024-03-27)

Primary citation

Xin, J.,Xu, Z.,Wang, X.,Tian, Y.,Zhang, Z.,Cai, G.
Structural basis of allosteric regulation of Tel1/ATM kinase.
Cell Res., 29:655-665, 2019

PubMed Abstract: ATM/Tel1 is an apical kinase that orchestrates the multifaceted DNA damage response. Mutations of ATM/Tel1 are associated with ataxia telangiectasia syndrome. Here, we report cryo-EM structures of symmetric dimer (4.1 Å) and asymmetric dimer (4.3 Å) of Saccharomyces cerevisiae Tel1. In the symmetric state, the side chains in Tel1 C-terminus (residues 1129-2787) are discernible and an atomic model is built. The substrate binding groove is completely embedded in the symmetric dimer by the intramolecular PRD and intermolecular LID domains. Point mutations in these domains sensitize the S. cerevisiae cells to DNA damage agents and hinder Tel1 activation due to reduced binding affinity for its activator Xrs2/Nbs1. In the asymmetric state, one monomer becomes more compact in two ways: the kinase N-lobe moves down and the Spiral of α-solenoid moves upwards, which resemble the conformational changes observed in active mTOR. The accessibility of the activation loop correlates with the synergistic conformational disorders in the TRD1-TRD2 linker, FATC and PRD domains, where critical post-translational modifications and activating mutations are coincidently condensed. This study reveals a tunable allosteric network in ATM/Tel1, which is important for substrate recognition, recruitment and efficient phosphorylation.

PubMed: 31097817
DOI: 10.1038/s41422-019-0176-1

Experimental method

ELECTRON MICROSCOPY (4.1 Å)