Fig. 2: Crystal structure of human TWSG1 in complex with Growth differentiation factor 5 (GDF5).

A Crystal structure of the TWSG1–GDF5 complex. The two views of the dimer differ by a 90° rotation around a horizontal axis. The disulfide-linked GDF5 dimer is colored in dark and light blue. The two TWSG1 NTDs are colored in orange and wheat. Calcium ions are shown as green spheres. B The side chain of TWSG1 Ile40 inserts into the hydrophobic pocket formed by two GDF5 protomers. Side chains of key residues are shown as sticks with oxygen and nitrogen atoms colored in red and blue, respectively. C Calcium-binding site forming interface contacts between TWSG1 and GDF5. Water molecules are shown as red spheres. Distances (Å) between selected atoms and GDF5 Trp414-Trp417 rings (T-shaped π-π stacking) are indicated with gray dashed lines. D–F Structures of GDF5 in complex with the BMPR1B ectodomain (D; PDB ID 3EVS)²⁵, the co-receptor RGMB (E; PDB ID 6Z3J)¹¹, and BMP9 in complex with its pro-___domain (F; PDB ID 4YCG)²⁶. GDF5 and BMP9 are shown in the same orientation as in A. G–I Close-up views of the interfaces for the complexes shown in D–F. In all cases, interactions are mediated by a hydrophobic side chain exposed on the α-helix of the GDF5/BMP9-binding partner and a hydrophobic pocket formed by the two GDF5/BMP9 protomers. This mode of interaction is also observed in the TWSG1–GDF5 complex (shown in B).