The face of TSR revealed: an extracellular signaling domain is exposed

In this issue, Tan et al. (2002) report the first high resolution (1.9 Å) structural data for thrombospondin (TSP)-1, a large multifunctional protein that regulates cell adhesion, angiogenesis, cell proliferation and survival, TGFβ activation, and protease function (for review see Chen et al., 2000). Because TSP-1 has multiple binding partners and many functions, precise structural information is crucial to understanding its biology. The structure now reported, derived from crystals of the second and third type I repeats of TSP-1 is of particular interest because of the specific functions attributed to these repeats and because domains homologous to the repeats appear in many other proteins in nature. The novel layered fold motif described brings great insight into how the complicated functions of TSP-1 and related molecules are affected.