9I91

Ku from Mycobacterium tuberculosis bound to DNA

Summary for 9I91

• Entry DOI: 10.2210/pdb9i91/pdb
• EMDB information: 52748
• Descriptor: Non-homologous end joining protein Ku, DNA 1, DNA 2, ... (4 entities in total)
• Functional Keywords: dna repair, tuberculosis, nhej, dna binding protein
• Biological source: Mycobacterium tuberculosis; More
• Total number of polymer chains: 10
• Total formula weight: 240236.71

Authors

Chaplin, A.K.,Zahid, S. (deposition date: 2025-02-06, release date: 2025-12-10)

Primary citation

Zahid, S.,Baconnais, S.,Smith, H.,Atwal, S.,Bates, L.,Read, H.,Chadda, A.,Morati, F.,Bedwell, T.,Stender, E.G.P.,Walter, J.,Hardwick, S.W.,Westerlund, F.,Galburt, E.,Le Cam, E.,Pyne, A.,Mukamolova, G.V.,Chaplin, A.K.
Oligomerisation of Ku from Mycobacterium tuberculosis promotes DNA synapsis.
Nat Commun, 16:10568-10568, 2025

PubMed Abstract: Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is estimated to infect nearly one-quarter of the global population. A key factor in its resilience and persistence is its robust DNA repair capacity. Non-homologous end joining (NHEJ) is the primary pathway for repairing DNA double-strand breaks (DSBs) in many organisms, including Mtb, where it is mediated by the Ku protein and the multifunctional LigD enzyme. In this study, we demonstrate that Ku is essential for mycobacterial survival under DNA-damaging conditions. Using cryogenic electron microscopy (cryo-EM), we solved high-resolution structures of both the apo and DNA-bound forms of the Ku-Mtb homodimer. Our structural and biophysical analyses reveal that Ku forms an extended proteo-filament upon binding DNA. We identify critical residues involved in filament formation and DNA synapsis and show that their mutation severely impairs bacterial viability. Furthermore, we propose a model in which the C-terminus of Ku regulates DNA binding and loading and facilitates subsequent recruitment of LigD. These findings provide unique insights into bacterial DNA repair and guide future therapeutics.

PubMed: 41298423
DOI: 10.1038/s41467-025-65609-y

Experimental method

ELECTRON MICROSCOPY (2.96 Å)