7ldg

Crystal structure of the MEILB2-BRCA2 complexCrystal structure of the MEILB2-BRCA2 complex

Structural highlights

7ldg is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.56Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

HSF2B_HUMAN The disease is caused by variants affecting the gene represented in this entry.

Function

HSF2B_HUMAN 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 (By similarity) (PubMed:31242413). 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 (By similarity). Required for proper recombinase recruitment in female meiosis (By similarity). Inhibits BNC1 transcriptional activity during spermatogenesis, probably by sequestering it in the cytoplasm (By similarity). May be involved in modulating HSF2 activation in testis (PubMed:9651507).[UniProtKB:Q9D4G2]^[1] ^[2]

Publication Abstract from PubMed

Meiotic cells invoke breast cancer susceptibility gene 2 (BRCA2) to repair programmed double-stranded DNA breaks and accomplish homologous recombination. The meiosis-specific protein MEILB2 facilitates BRCA2 recruitment to meiotic recombination sites. Here, we combine crystallography, biochemical analysis and a mouse meiosis model to reveal a robust architecture that ensures meiotic BRCA2 recruitment. The crystal structure of the MEILB2-BRCA2 complex reveals how two MEILB2 homodimers sandwich two chains of BRCA2 to afford a 4:2 architecture. The sandwich lacks close contact between the two MEILB2 dimers or the two BRCA2 chains. Instead, the two halves of each BRCA2 chain bridge two MEILB2 subunits from different homodimers to form the MEILB2-BRCA2-MEILB2 sandwich. Several identical residues from the two MEILB2 subunits are employed to engage the BRCA2 halves, justifying their strict conservation. Mutational analysis of the interface reveals a synergistic mechanism for MEILB2-BRCA2 recruitment during meiosis. Overall, these studies demonstrate how BRCA2 efficiently localizes in the cell to facilitate meiosis.

Structure of a meiosis-specific complex central to BRCA2 localization at recombination sites.,Pendlebury DF, Zhang J, Agrawal R, Shibuya H, Nandakumar J Nat Struct Mol Biol. 2021 Aug;28(8):671-680. doi: 10.1038/s41594-021-00635-0. , Epub 2021 Aug 9. PMID:34373645^[3]

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

References

↑ 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
↑ Yoshima T, Yura T, Yanagi H. Novel testis-specific protein that interacts with heat shock factor 2. Gene. 1998 Jul 3;214(1-2):139-46. PMID:9651507 doi:10.1016/s0378-1119(98)00208-x
↑ Pendlebury DF, Zhang J, Agrawal R, Shibuya H, Nandakumar J. Structure of a meiosis-specific complex central to BRCA2 localization at recombination sites. Nat Struct Mol Biol. 2021 Aug;28(8):671-680. PMID:34373645 doi:10.1038/s41594-021-00635-0

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OCA

[1] 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

[2] Yoshima T, Yura T, Yanagi H. Novel testis-specific protein that interacts with heat shock factor 2. Gene. 1998 Jul 3;214(1-2):139-46. PMID:9651507 doi:10.1016/s0378-1119(98)00208-x

[3] Pendlebury DF, Zhang J, Agrawal R, Shibuya H, Nandakumar J. Structure of a meiosis-specific complex central to BRCA2 localization at recombination sites. Nat Struct Mol Biol. 2021 Aug;28(8):671-680. PMID:34373645 doi:10.1038/s41594-021-00635-0

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