GPVI binding to fibrillar collagen requires a large distance between receptor molecules. (A) Schematic representations of GPVI binding (blue) to a triple helix (magenta) embedded in a collagen fibril (left panel) or immobilized onto a flat surface (right panel), illustrating that the circumferential angular range available for GPVI binding is about 200° and 250°, respectively. Additional GPVI molecules, covering about 160°, therefore need to bind at the same side of a helix or parallel helix. Triple-helical packing displayed in the left panel was taken from the in situ structure of collagen I, which exhibits a parallel helix packing leading to surface exposure of identical binding sites on parallel helices.³⁴ (B) Perpendicular views of two GPVI molecules (blue and salmon) binding to identical sites on parallel helices (magenta) with minimum 34 Å spacing, showing its bent shape and oblique orientation with respect to the collagen helix preclude binding to closer-spaced helices. (C) Perpendicular views of the two GPVI molecules (blue and salmon) bound to (GPO)₅ as observed in our crystal structure. A short center-to-center distance of only 16 Å (left panel) is accompanied by a large circumferential coverage of about 310° (right panel), which is not feasible if the helix is incorporated in the fibril or immobilized on a surface. See also supplemental Figure 9. (D) Perpendicular views of putative arrangements of two GPVI molecules (blue and salmon) bound to a triple helix in a 7₂ (top and bottom, magenta) or 10₃ (middle, orange) conformation. Their circumferential coverage angles are within the maximum value of 200° available for binding to fibrillar collagen; their center-to-center distance ranges from 32 to 40 Å, at least twofold larger than the distance observed in crystal structures. See also supplemental Figure 10 and supplemental Methods for details about modeling.