7z8z

From Proteopedia

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

Structural highlights

7z8z is a 4 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.5Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HSF2B_MOUSE Meiotic recombination factor component of recombination bridges involved in meiotic double-strand break repair. Modulates the localization of recombinases DMC1:RAD51 to meiotic double-strand break (DSB) sites through the interaction with BRCA2 and its recruitment during meiotic recombination. Indispensable for the DSB repair, homologous synapsis, and crossover formation that are needed for progression past metaphase I, is essential for spermatogenesis and male fertility (PubMed:30760716, PubMed:31242413, PubMed:32345962, PubMed:32463460). Required for proper recombinase recruitment in female meiosis (PubMed:30760716, PubMed:32845237). Inhibits BNC1 transcriptional activity during spermatogenesis, probably by sequestering it in the cytoplasm (PubMed:23707421). May be involved in modulating HSF2 activation in testis (By similarity).[UniProtKB:O75031]^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

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 beta-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 beta-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.

MEILB2-BRME1 forms a V-shaped DNA clamp upon BRCA2-binding in meiotic recombination.,Gurusaran M, Zhang J, Zhang K, Shibuya H, Davies OR Nat Commun. 2024 Aug 2;15(1):6552. doi: 10.1038/s41467-024-50920-x. PMID:39095423^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wu Y, Liao S, Wang X, Wang S, Wang M, Han C. HSF2BP represses BNC1 transcriptional activity by sequestering BNC1 to the cytoplasm. FEBS Lett. 2013 Jul 11;587(14):2099-104. PMID:23707421 doi:10.1016/j.febslet.2013.04.049
↑ Zhang J, Fujiwara Y, Yamamoto S, Shibuya H. A meiosis-specific BRCA2 binding protein recruits recombinases to DNA double-strand breaks to ensure homologous recombination. Nat Commun. 2019 Feb 13;10(1):722. PMID:30760716 doi:10.1038/s41467-019-08676-2
↑ Brandsma I, Sato K, van Rossum-Fikkert SE, van Vliet N, Sleddens E, Reuter M, Odijk H, van den Tempel N, Dekkers DHW, Bezstarosti K, Demmers JAA, Maas A, Lebbink J, Wyman C, Essers J, van Gent DC, Baarends WM, Knipscheer P, Kanaar R, Zelensky AN. HSF2BP Interacts with a Conserved Domain of BRCA2 and Is Required for Mouse Spermatogenesis. Cell Rep. 2019 Jun 25;27(13):3790-3798.e7. PMID:31242413 doi:10.1016/j.celrep.2019.05.096
↑ Zhang J, Gurusaran M, Fujiwara Y, Zhang K, Echbarthi M, Vorontsov E, Guo R, Pendlebury DF, Alam I, Livera G, Emmanuelle M, Wang PJ, Nandakumar J, Davies OR, Shibuya H. The BRCA2-MEILB2-BRME1 complex governs meiotic recombination and impairs the mitotic BRCA2-RAD51 function in cancer cells. Nat Commun. 2020 Apr 28;11(1):2055. PMID:32345962 doi:10.1038/s41467-020-15954-x
↑ Shang Y, Huang T, Liu H, Liu Y, Liang H, Yu X, Li M, Zhai B, Yang X, Wei Y, Wang G, Chen Z, Wang S, Zhang L. MEIOK21: a new component of meiotic recombination bridges required for spermatogenesis. Nucleic Acids Res. 2020 Jul 9;48(12):6624-6639. PMID:32463460 doi:10.1093/nar/gkaa406
↑ Felipe-Medina N, Caburet S, Sánchez-Sáez F, Condezo YB, de Rooij DG, Gómez-H L, Garcia-Valiente R, Todeschini AL, Duque P, Sánchez-Martin MA, Shalev SA, Llano E, Veitia RA, Pendás AM. A missense in HSF2BP causing primary ovarian insufficiency affects meiotic recombination by its novel interactor C19ORF57/BRME1. Elife. 2020 Aug 26;9:e56996. PMID:32845237 doi:10.7554/eLife.56996
↑ Gurusaran M, Zhang J, Zhang K, Shibuya H, Davies OR. MEILB2-BRME1 forms a V-shaped DNA clamp upon BRCA2-binding in meiotic recombination. Nat Commun. 2024 Aug 2;15(1):6552. PMID:39095423 doi:10.1038/s41467-024-50920-x