7Z8Z

Crystal structure of the MEILB2-BRME1 2:2 core complex

Summary for 7Z8Z

• Entry DOI: 10.2210/pdb7z8z/pdb
• Descriptor: Heat shock factor 2-binding protein, Break repair meiotic recombinase recruitment factor 1 (3 entities in total)
• Functional Keywords: meiosis, dna repair, dna clamp, double-strand break, recombination
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 4
• Total formula weight: 23895.85

Authors

Gurusaran, M.,Davies, O.R. (deposition date: 2022-03-19, release date: 2023-09-20, Last modification date: 2024-08-14)

Primary citation

Gurusaran, M.,Zhang, J.,Zhang, K.,Shibuya, H.,Davies, O.R.
MEILB2-BRME1 forms a V-shaped DNA clamp upon BRCA2-binding in meiotic recombination.
Nat Commun, 15:6552-6552, 2024

PubMed Abstract: DNA double-strand break repair by homologous recombination has a specialised role in meiosis by generating crossovers that enable the formation of haploid germ cells. This requires meiosis-specific MEILB2-BRME1, which interacts with BRCA2 to facilitate loading of recombinases onto resected DNA ends. Here, we report the crystal structure of the MEILB2-BRME1 2:2 core complex, revealing a parallel four-helical assembly that recruits BRME1 to meiotic double-strand breaks in vivo. It forms an N-terminal β-cap that binds to DNA, and a MEILB2 coiled-coil that bridges to C-terminal ARM domains. Upon BRCA2-binding, MEILB2-BRME1 2:2 complexes dimerize into a V-shaped 2:4:4 complex, with rod-like MEILB2-BRME1 components arranged at right-angles. The β-caps located at the tips of the MEILB2-BRME1 limbs are separated by 25 nm, allowing them to bridge between DNA molecules. Thus, we propose that BRCA2 induces MEILB2-BRME1 to function as a DNA clamp, connecting resected DNA ends or homologous chromosomes to facilitate meiotic recombination.

PubMed: 39095423
DOI: 10.1038/s41467-024-50920-x

Experimental method

X-RAY DIFFRACTION (1.5 Å)