PMID: 15014436

 

    Legend: Sugar

Title : Structure of a thrombospondin C-terminal fragment reveals a novel calcium core in the type 3 repeats

Abstract :
  1. Thrombospondins ( TSPs ) are extracellular regulators of cell-matrix interactions and cell phenotype
  2. The most highly conserved region of all TSPs are the calcium-binding type 3 (T3) repeats and the C-terminal globular domain (CTD)
  3. The crystal structure of a cell-binding TSP-1 fragment , spanning three T3 repeats and the CTD, reveals a compact assembly
  4. 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
  5. The CTD forms a lectin-like beta-sandwich and contains four strictly conserved calcium-binding sites
  6. Disruption of the hairpin structure of T3 repeats 6 and 7 decreases protein secretion and stability
  7. The availability for cell attachment of an RGD motif in T3 repeat 7 is modulated by calcium loading
  8. The central architectural role of calcium explains how it is critical for the functions of the TSP C-terminal region
  9. 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