2OUJ

The crystal structure of the Thrombospondin-1 N-terminal domain in complex with fractionated Heparin DP8

2OUJ の概要

• エントリーDOI: 10.2210/pdb2ouj/pdb
• 関連するPDBエントリー: 1Z78 1ZA4 2OUH
• 分子名称: Thrombospondin-1 (2 entities in total)
• 機能のキーワード: tsp-1, tspn-1, hbd, fractionated heparin, dp8, cell adhesion
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 27556.10

構造登録者

Tan, K.,Joachimiak, A.,Wang, J.,Lawler, J. (登録日: 2007-02-11, 公開日: 2008-01-08, 最終更新日: 2024-11-13)

主引用文献

Tan, K.,Duquette, M.,Liu, J.H.,Shanmugasundaram, K.,Joachimiak, A.,Gallagher, J.T.,Rigby, A.C.,Wang, J.H.,Lawler, J.
Heparin-induced cis- and trans-Dimerization Modes of the Thrombospondin-1 N-terminal Domain.
J.Biol.Chem., 283:3932-3941, 2008

PubMed Abstract: Through its interactions with proteins and proteoglycans, thrombospondin-1 (TSP-1) functions at the interface of the cell membrane and the extracellular matrix to regulate matrix structure and cellular phenotype. We have previously determined the structure of the high affinity heparin-binding domain of TSP-1, designated TSPN-1, in association with the synthetic heparin, Arixtra. To establish that the binding of TSPN-1 to Arixtra is representative of the association with naturally occurring heparins, we have determined the structures of TSPN-1 in complex with heparin oligosaccharides containing eight (dp8) and ten (dp10) subunits, by x-ray crystallography. We have found that dp8 and dp10 bind to TSPN-1 in a manner similar to Arixtra and that dp8 and dp10 induce the formation of trans and cis TSPN-1 dimers, respectively. In silico docking calculations partnered with our crystal structures support the importance of arginine residues in positions 29, 42, and 77 in binding sulfate groups of the dp8 and dp10 forms of heparin. The ability of several TSPN-1 domains to bind to glycosaminoglycans simultaneously probably increases the affinity of binding through multivalent interactions. The formation of cis and trans dimers of the TSPN-1 domain with relatively short segments of heparin further enhances the ability of TSP-1 to participate in high affinity binding to glycosaminoglycans. Dimer formation may also involve TSPN-1 domains from two separate TSP-1 molecules. This association would enable glycosaminoglycans to cluster TSP-1.

PubMed: 18065761
DOI: 10.1074/jbc.M705203200

実験手法

X-RAY DIFFRACTION (1.9 Å)