Title : Structure of a thrombospondin C-terminal
fragment reveals a novel calcium core in
the type 3 repeats
Abstract :
- Thrombospondins ( TSPs ) are extracellular regulators of cell-matrix interactions and cell phenotype
- The most highly conserved region of all TSPs are the calcium-binding type 3 (T3) repeats and the C-terminal globular domain (CTD)
- The crystal structure of a cell-binding TSP-1 fragment , spanning three T3 repeats and the CTD, reveals a compact assembly
- The T3 repeats lack secondary structure and are organised around a core of calcium ions; two DxDxDGxxDxxD motifs per repeat each encapsulate two calcium ions in a novel arrangement
- The CTD forms a lectin-like beta-sandwich and contains four strictly conserved calcium-binding sites
- Disruption of the hairpin structure of T3 repeats 6 and 7 decreases protein secretion and stability
- The availability for cell attachment of an RGD motif in T3 repeat 7 is modulated by calcium loading
- The central architectural role of calcium explains how it is critical for the functions of the TSP C-terminal region
- Mutations in the T3 repeats of TSP-5/ COMP , which cause two human skeletal disorders, are predicted to disrupt the tertiary structure of the T3-CTD assembly