5Z78

Structure of TIRR/53BP1 complex

Summary for 5Z78

• Entry DOI: 10.2210/pdb5z78/pdb
• Descriptor: Tudor-interacting repair regulator protein, TP53-binding protein 1 (3 entities in total)
• Functional Keywords: dna repair protein, transcription-protein binding complex, transcription/protein binding
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 3
• Total formula weight: 60444.81

Authors

Dai, Y.X.,Shan, S. (deposition date: 2018-01-27, release date: 2018-06-06, Last modification date: 2023-11-22)

Primary citation

Dai, Y.,Zhang, A.,Shan, S.,Gong, Z.,Zhou, Z.
Structural basis for recognition of 53BP1 tandem Tudor domain by TIRR
Nat Commun, 9:2123-2123, 2018

PubMed Abstract: P53-binding protein 1 (53BP1) regulates the double-strand break (DSB) repair pathway choice. A recently identified 53BP1-binding protein Tudor-interacting repair regulator (TIRR) modulates the access of 53BP1 to DSBs by masking the H4K20me2 binding surface on 53BP1, but the underlying mechanism remains unclear. Here we report the 1.76-Å crystal structure of TIRR in complex with 53BP1 tandem Tudor domain. We demonstrate that the N-terminal region (residues 10-24) and the L8-loop of TIRR interact with 53BP1 Tudor through three loops (L1, L3, and L1'). TIRR recognition blocks H4K20me2 binding to 53BP1 Tudor and modulates 53BP1 functions in vivo. Structure comparisons identify a TIRR histidine (H106) that is absent from the TIRR homolog Nudt16, but essential for 53BP1 Tudor binding. Remarkably, mutations mimicking TIRR binding modules restore the disrupted binding of Nudt16-53BP1 Tudor. Our studies elucidate the mechanism by which TIRR recognizes 53BP1 Tudor and functions as a cellular inhibitor of the histone methyl-lysine readers.

PubMed: 29844495
DOI: 10.1038/s41467-018-04557-2

Experimental method

X-RAY DIFFRACTION (1.762 Å)