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. 2023 Mar 28;141(25):3109–3121. doi: 10.1182/blood.2022019359

Figure 6.

Figure 6.

Structure of the C3bB-lufaxin-fXa complex. (A) Cryo-EM reconstruction of the complex with C3b, FB, and lufaxin colored as in Figure 1C, with the SP domain of fXa in light green and the light chain of fXa in magenta. Domain features of the complex are labeled. (B) The map of panel A colored by local resolution (calculated using Phenix) per the color key shown below the map. (C) Ribbon diagram of the fXa-SP domain (light green) and lufaxin (light blue) portions of the complex highlighting key features of the interface, including the C-terminal coil of lufaxin, the autolysis loop of fXa and the 220 loop of fXa. (D) Surfaces of fXa-SP domain (light green) and lufaxin (light blue) rotated around the vertical axis to show the binding interface determined by PISA. Interface residues on lufaxin are colored light green, and those on fXa-SP are colored light blue. Arg 277 of lufaxin, which interacts with the S1 subsite of fXa, is colored magenta, with nitrogen atoms in blue. The catalytic serine residue (Ser 195) of fXa is colored red. (E) Details of interactions between the C-terminal domain of lufaxin (light blue) with the SP domain of fXa (light green), with the fXa portion also shown as a semitransparent surface. Individual side chains are shown as sticks, with oxygen colored red and nitrogen colored blue. Lufaxin side chains are labeled in light blue, and fXa side chains interacting with the lufaxin surface are labeled in light green. Residues of the fXa catalytic triad (His 57, Asp 102, and Ser 195) are colored in cyan and labeled in black. The C-terminal coil structure of lufaxin-containing Arg 277 is labeled. (F) Ribbon diagram of the lufaxin-fXa-SP magnified to show electrostatic interactions of Arg 277 of lufaxin (light blue, with oxygen colored red and nitrogen blue) with residues of the S1 subsite at the active site of fXa (light green). The catalytic serine (Ser 195) of fXa is colored cyan. Hydrogen bonds and salt bridges are shown as red dashed lines. (G) Lufaxin interactions with the autolysis loop and 220 loop of fXa-SP detailed as in panel F.