Fig. 2: Crystal structure of the MEILB2α–BRME1MBD 2:2 core complex.
From: MEILB2-BRME1 forms a V-shaped DNA clamp upon BRCA2-binding in meiotic recombination
a Schematic of mouse BRCA2, MEILB2 and BRME1 sequences, highlighting domains, interaction sites and constructs used in this study. BRCA2 includes recombinase-binding BRC repeats, a MEILB2-binding domain (MBD), DMC1-binding exon 14, a DNA-binding domain (DBD) and RAD51-binding exon 27. MEILB2 contains a BRME1-binding α-helical region, and a BRCA2-binding armadillo repeat (ARM) domain. BRME1 has a MEILB2-binding domain (MBD). b Crystal structure of the MEILB2α–BRME1MBD 2:2 core complex. MEILB2 α1 (blue) and BRME1 (yellow) α-helices interact within a parallel four-helical bundle. MEILB2 α1 helices are followed by kinks that re-orientate α2 helices to form a parallel dimeric coiled-coil, and are preceded by a β-cap. c The N-terminal β-cap is a two-stranded anti-parallel β-sheet that is oriented perpendicular to the coiled-coil axis, supported by hydrophobic interactions of MEILB2 F24 and K26 and BRME1 M541. d The hydrophobic core of the parallel four-helical bundle is formed of leucine, isoleucine and valine amino acids of MEILB2 and BRME1 chains, as indicated. e The kink within the MEILB2 chain is defined by non-helical backbone torsion angles of L50 and N51 (left), and a single amino-acid insertion between heptad repeats of α1 and α2 helices (indicated by an arrow, right). Multiple sequence alignment: Mus musculus (Mm), Homo sapiens (Hs), Mesocricetus auratus (Ma), Gallus gallus (Gg), Callorhinchus milii (Cm) and Xenopus tropicalis (Xt). The full alignment is shown in Supplementary Fig. 1a. f The MEILB2 α2 parallel dimeric coiled-coil is formed of ‘a’ and ‘d’ heptad amino-acids L54, S57, L61, V64, L68, K71 and L75. g Schematic of the MEILB2α–BRME1MBD 2:2 core structure.
