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==Overview== | ==Overview== | ||
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. | 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. | ||
==Disease== | |||
Known disease associated with this structure: Sudden infant death with dysgenesis of the testes syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604714 604714]] | |||
==About this Structure== | ==About this Structure== | ||
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[[Category: l-type lectin]] | [[Category: l-type lectin]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:39:31 2007'' | ||