Extended Data Fig. 7: Glu-rich regions of VKDPs.
From: Molecular basis of vitamin-K-driven γ-carboxylation at the membrane interface
a, VKGC binding interactions with the 5-AA Glu-containing segments from FIX, FX, TMG2, and PC. b, Electrostatic surface showing the binding grooves for individual side chains in the 5-AA segments. These interactions are highly adaptive to different Glu-containing sequences. c, Sequence alignment of the Glu-rich regions from human VKDPs. OCN, GRP, and MGP are shown separately due to their low sequence homology to other VKDPs in the Gla domain. The dots in MGP indicate position of the propeptide that is flanked by Glu-rich sequences. For clarity, the non-consensus Glu residues in OCN, MGP, and GRP, and those at the C-terminal (after +33) of other VKDPs are shown in red letters, and those known to be carboxylated in bold. The sequence alignments were generated by Clustal W v2.1. The grey and light grey shading denote highly and moderately conserved residues, respectively. The sequence logos89 above alignments depict the residue conservation level at each position. Secondary structures (ω-loop and helices h1, h2, and h3) and disulfide bond (S-S) in the Gla domain are indicated below. Inset, Structural location of the Gla residues, Ca2+ ions, and hydrophobic residues (in ω-loop). The crystal structure of human FIX Gla domain (PDB 1NL0)88 is shown with membrane (grey shading) insertion90.
