Mutations within the αIIb calcium-binding domains.

(Left) Schematic of the β-propeller domain of αIIb and αv showing the central cage motif. The blades are labeled W1 through W7. The cage motif comprises 2 concentric rings of predominantly aromatic residues, which line the upper, inner rim of the propeller core. Each blade contributes 2 residues to the cage structure, represented here by hexagons. (Right) Schematic of one blade of the αIIb β-propeller derived from molecular modeling, showing the relative locations of 7 Glanzmann thrombasthenia mutations that lie within blades W4-W7. The blade is viewed from the side, with the 2 cage residues indicated and the calcium-binding loop at the bottom. Starting from the cage residues, the 4 antiparallel β-strands of the blade form the legs of a “W.” Seven mutations reported to be in or near the calcium-binding domains (including the 2 from this study, underlined) are shown in their relative positions: Gly273Asp from W4; Val298Phe, Glu324Lys, and Arg327His from W5; Ile374Thr from W6; and Gly418Asp and deletion Val425/Asp426 from W7.7-11