Fig. 1: An unexpected IP₆-binding site in the Drosophila IntS4-IntS9-IntS11 complex (ICM).

a Domain organizations of Drosophila IntS4, IntS9, and IntS11. The domains are named and given different colors. The domains of IntS9 are shown in slightly darker colors compared to IntS11. Residues observed in the structure of the IntS4-IntS9-IntS11 complex are indicated with the red lines. The vertical bars in blue represent positively charged residues in the IP₆ binding site. ICM Integrator cleavage module, NTD N-terminal domain, MD middle domain, CTD C-terminal domain, MβL metallo-β-lactamase, β-CASP metallo-β-lactamase-associated CPSF, Artemis, SNM1/PSO2. b Gel filtration profile of Drosophila ICM. Inset: SDS gel of the purified complex. The experiment was done at least three times with similar results. c The overall structure of the Drosophila ICM. The domains are colored as in panel a and labeled. The IP₆ molecule is shown as stick models (black for carbon atoms). d Another view of the structure of the IntS4-IntS9-IntS11 complex, related to that of panel c by a 90° rotation around the vertical axis. e Overlay of the dimer of the metallo-β-lactamase and β-CASP domains of IntS9-IntS11 (in color) in the ICM with the dimer of the equivalent domains of human CPSF100-CPSF73 (gray) in the active histone pre-mRNA 3′-end processing machinery. The pseudo two-fold axis of this dimer is along the vertical direction (indicated with the black line). The CTD1s of the two structures assume very different positions, and the CTD2s are not shown. IntS9 metallo-β-lactamase domain contains two insertions, residues 34–83 (labeled 1) and 150–179 (2), that are positioned next to the β-CASP domain. The structure figures were produced with PyMOL (www.pymol.org) unless otherwise indicated.