Location of amino acid mutations impairing GPIbα, heparin, and AJvW-2 binding to VWF A1.

Space-filling, 3-dimensional representation of the human VWF A1 domain. (A) Front (left) and back (right) view of the A1 domain. Surface residues of mutations previously shown to abolish shear-dependent platelet interactions with the recombinant VWF A1 domain16,19 20 or to cause VWD type 2M (ISTH SSC VWF database: www.shef.ac.uk/vwf/) are indicated in orange. Location of buried residues is indicated by dotted lines. Amino acid substitutions detected in type 2M VWD patients are underlined. For space considerations, single-letter codes were used for amino acids. (B) Surface residues of mutations in the present study that impaired the shear-dependent interaction of the VWF A1 domain with platelet GPIbα are indicated in red. The location of the buried residue Ala618 is indicated by a dotted line. (C) Residues of mutations in the present study that impaired heparin and AJvW-2 recognition are indicated in blue. Amino acid Ala587, whose mutation only impairs AJvW-2 binding, is indicated in cyan. Pictures were created with RasMol v2.6.