Fig. 3: The same conserved ARM surface interacts with both the N-terminal and C-terminal regions of the BRCA2 peptide, through a 23 aa motif.

a Superimposition of the complexes formed by two ARM domains and a BRCA2 peptide. The Cα root-mean-square-deviation (Rmsd) values calculated between the different chains are recapitulated in the lower part of the panel. Additional views of the superimposed individual chains are displayed in Supplementary Fig. 7. b Zoom on the interfaces between ARM chain B and the C-terminal region of BRCA2 F15X chain F (upper view) and ARM chain D and the N-terminal region of BRCA2 F15X chain F (lower view). ARM residues that are either involved in hydrogen bonds or salt bridges with BRCA2, or buried (by more than 30 Ų) at the interface with BRCA2, are represented by colored sticks. They are labeled in Supplementary Fig. 7b, c. c Surfaces of ARM domains, colored as a function of sequence conservation (upper panel) or electrostatic potential (lower panel). In the upper panel, surfaces of ARM chains B and D are colored as a function of conservation scores calculated by Consurf⁶⁵. High, medium, weak, and no conservation are indicated in dark blue, cyan, green, and gray, respectively. BRCA2 F15X F is represented as a red ribbon. In the lower panel, the surface of ARM chain D is colored from red (negatively charged) to blue (positively charged) and the N-terminal region of BRCA2 F15X F is displayed as a black ribbon. d Superimposition of the four ARM domains and their BRCA2-interacting peptides. The four ARM structures were aligned, and their BRCA2-interacting fragments are displayed. e Representation of the 3D structure of the BRCA2 motif binding to ARM domains. Residues strictly conserved between motif 1 and motif 2 are displayed as olive sticks. They correspond to D2294/2317, R2295/2318, S2303/2326, L2304/2327, and P2311/2334. Residues that are similar between the two motifs and conserved in BRCA2 are displayed as brown sticks. They correspond to A2306/P2329 and S2309/C2332 (mutated in T2332 in our construct to avoid oxidation of this residue). A set of conserved residues from ARM interacting with BRCA2, as defined in b, are indicated in black next to the BRCA2 residues when they directly interact with these residues. A boxed surface view of the peptide, in the same orientation as the cartoon view, is colored by conservation as in c. Turning this surface view by 180° reveals the conservation of the surface binding to ARM, including the conserved residues of motifs 1 and 2. f Sequence alignment of motif 1, interacting with ARM chains C and D, and motif 2, interacting with ARM chains A and B. Conserved residues are colored as in e. Motif 1 is encoded by exon 12, whereas motif 2 is encoded by exon 13.