Fig. 2. Three prominent dimer interfaces of the Mec1-Ddc2 complex.
(A) Cryo-EM structure of the Mec1-Ddc2 homodimer highlighting the three
dimer interfaces. Two monomers are respectively displayed in surface and mesh.
The interfaces of Mec1-Ddc2 are color-coded: PRD in red, TRD2 domain in
cyan, TRD3 domain in purple, a-solenoids in orange, and Ddc2 in light
green. (B) Enlarged view of the PRD-PRD and PRD-TRD3 interface. The
potential hydrogen bonds are denoted by black dashed lines. (C) Enlarged
view of the TRD2-TRD2 and TRD2-TRD3 interface. The intermolecular
hydrogen bonds between the TRD2 and TRD3 domains are denoted by
black dashed lines. (D) Enlarged view of the Ddc2-Ddc2 interface.
The side chain of Leu residues mediating putative hydrophobic
interactions is shown. The potential electrostatic interactions at the
bottom loop are denoted by black dashed lines. (E) Enlarged view of the
Mec1 a-solenoid–Ddc2 interface. The potential hydrogen bonds are
denoted by black dashed lines. Amino acid abbreviations appearing here
or in other figures: A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; G, Gly; H, His;
I, Ile; K, Lys; L, Leu; M, Met; N, Asn; P, Pro; Q, Gln; R, Arg; S, Ser; T, Thr;
V, Val; W, Trp; Y, Tyr.
Fig. 1. Architecture of Mec1-Ddc2. (A) Front view of the density map of
the Mec1-Ddc2 homodimer at 3.9 Å. One monomer is color-coded by
domain assignment: FAT-KD-PRD-FATC in blue, N-terminal a-solenoid in
orange, and Ddc2 in light green. The other monomer is shown as a solid
gray surface. (B) Bottom view of the density map. (C) Three views of the
Mec1-Ddc2 monomer. The cryo-EM density is shown as a translucent
surface and fitted with the ribbon diagram model. The N-terminal a-solenoids
of Mec1 are in orange, FAT in cornflower blue, kinase N-lobe in yellow,
C-lobe in hot pink, PRD in red, and FATC in blue. Also shown are the Bridge
of Mec1 in dark orange and Ddc2 in light green. Each successive view is
rotated as indicated. The red stars highlight the Thr1989 autophosphorylation
site in human ATR. (D) Schematic representation highlighting the
functional domains of Mec1 and Ddc2. The N-terminal checkpoint protein
recruitment domain (CRD) and Ddc2’s interface with Dpb11 are denoted.
Three units of Mec1 are labeled: the N-terminal a-solenoid and its Bridge
region; the FATregion (TRD1, 2, 3 and HRD); and the KD, PRD, and FATC. The
flexible regions controlling the Bridge domain and loops critical for Mec1
activity are shown above the schematic.