| Structural highlights
1yo8 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , ,
| | NonStd Res: | |
| Gene: | THBS2, TSP2 (Homo sapiens) |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[TSP2_HUMAN] Genetic variations in THBS2 may be a cause of susceptibility to intervertebral disk disease (IDD) [MIM:603932]; also known as lumbar disk herniation (LDH). IDD is one of the most common musculo-skeletal disorders and the predominant cause of low-back pain and unilateral leg pain.[1]
Function
[TSP2_HUMAN] Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. Ligand for CD36 mediating antiangiogenic properties.[2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Thrombospondins (THBSs) are secreted glycoproteins that have key roles in interactions between cells and the extracellular matrix. Here, we describe the 2.6-A-resolution crystal structure of the glycosylated signature domain of human THBS2, which includes three epidermal growth factor-like modules, 13 aspartate-rich repeats and a lectin-like module. These elements interact extensively to form three structural regions termed the stalk, wire and globe. The THBS2 signature domain is stabilized by these interactions and by a network of 30 bound Ca(2+) ions and 18 disulfide bonds. The structure suggests how genetic alterations of THBSs result in disease.
Structure of the calcium-rich signature domain of human thrombospondin-2.,Carlson CB, Bernstein DA, Annis DS, Misenheimer TM, Hannah BL, Mosher DF, Keck JL Nat Struct Mol Biol. 2005 Oct;12(10):910-4. Epub 2005 Sep 25. PMID:16186819[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hirose Y, Chiba K, Karasugi T, Nakajima M, Kawaguchi Y, Mikami Y, Furuichi T, Mio F, Miyake A, Miyamoto T, Ozaki K, Takahashi A, Mizuta H, Kubo T, Kimura T, Tanaka T, Toyama Y, Ikegawa S. A functional polymorphism in THBS2 that affects alternative splicing and MMP binding is associated with lumbar-disc herniation. Am J Hum Genet. 2008 May;82(5):1122-9. Epub 2008 May 1. PMID:18455130 doi:S0002-9297(08)00223-1
- ↑ Koch M, Hussein F, Woeste A, Grundker C, Frontzek K, Emons G, Hawighorst T. CD36-mediated activation of endothelial cell apoptosis by an N-terminal recombinant fragment of thrombospondin-2 inhibits breast cancer growth and metastasis in vivo. Breast Cancer Res Treat. 2011 Jul;128(2):337-46. doi: 10.1007/s10549-010-1085-7. , Epub 2010 Aug 17. PMID:20714802 doi:10.1007/s10549-010-1085-7
- ↑ Carlson CB, Bernstein DA, Annis DS, Misenheimer TM, Hannah BL, Mosher DF, Keck JL. Structure of the calcium-rich signature domain of human thrombospondin-2. Nat Struct Mol Biol. 2005 Oct;12(10):910-4. Epub 2005 Sep 25. PMID:16186819 doi:10.1038/nsmb997
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