1UX6

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

Summary for 1UX6

• Entry DOI: 10.2210/pdb1ux6/pdb
• Related: 1LSL
• Descriptor: THROMBOSPONDIN-1, CALCIUM ION (3 entities in total)
• Functional Keywords: extracellular matrix, calcium binding, l-type lectin, glycoprotein, cell adhesion, calcium-binding, heparin-binding, egf-like domain
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Endoplasmic reticulum : P07996
• Total number of polymer chains: 1
• Total formula weight: 40362.33

Authors

Kvansakul, M.,Adams, J.C.,Hohenester, E. (deposition date: 2004-02-19, release date: 2004-03-18, Last modification date: 2024-11-20)

Primary citation

Kvansakul, M.,Adams, J.C.,Hohenester, E.
Structure of a Thrombospondin C-Terminal Fragment Reveals a Novel Calcium Core in the Type 3 Repeats
Embo J., 23:1223-, 2004

PubMed 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.

PubMed: 15014436
DOI: 10.1038/SJ.EMBOJ.7600166

Experimental method

X-RAY DIFFRACTION (1.9 Å)