3R6B: Crystal Structure Of Thrombospondin-1 Tsr Domains 2 And 3

Citation:
Abstract
The matrix glycoprotein thrombospondin-1 (TSP-1) is a prominent regulator of endothelial cells and angiogenesis. The anti-angiogenic and anti-tumorigenic properties of TSP-1 are in part mediated by the TSP-1 type 1 repeat domains 2 and 3, TSR(2,3). Here, we describe the expression and purification of human TSR(2,3) in milligram quantities from an Escherichia coli expression system. Microvascular endothelial cell migration assays and binding assays with a canonical TSP-1 ligand, histidine-rich glycoprotein (HRGP), indicate that recombinant TSR(2,3) exhibits anti-chemotactic and ligand binding properties similar to full length TSP-1. Furthermore, we determined the structure of E. coli expressed TSR(2,3) by X-ray crystallography at 2.4A and found the structure to be identical to the existing TSR(2,3) crystal structure determined from a Drosophila expression system. The TSR(2,3) expression and purification protocol developed in this study allows for facile expression of TSR(2,3) for biochemical and biophysical studies, and will aid in the elucidation of the molecular mechanisms of TSP-1 anti-angiogenic and anti-tumorigenic activities.
PDB ID: 3R6BDownload
MMDB ID: 92551
PDB Deposition Date: 2011/3/21
Updated in MMDB: 2011/11
Experimental Method:
x-ray diffraction
Resolution: 2.4  Å
Source Organism:
Similar Structures:
Biological Unit for 3R6B: monomeric; determined by author and by software (PISA)
Molecular Components in 3R6B
Label Count Molecule
Protein (1 molecule)
1
Thrombospondin-1(Gene symbol: THBS1)
Molecule annotation
Chemicals (8 molecules)
1
8
* Click molecule labels to explore molecular sequence information.

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