2OYA

Crystal structure analysis of the dimeric form of the SRCR domain of mouse MARCO

2OYA の概要

• エントリーDOI: 10.2210/pdb2oya/pdb
• 関連するPDBエントリー: 2OY3
• 分子名称: Macrophage receptor MARCO, SULFATE ION (3 entities in total)
• 機能のキーワード: extracellular matrix, scavenger receptor cysteine-rich (srcr), macrophage receptor, ligand binding, basic cluster, acidic cluster, sulfate binding, dimer, ligand binding protein
• 由来する生物種: Mus musculus (house mouse)
• 細胞内の位置: Cell membrane ; Single-pass type II membrane protein : Q60754
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22962.75

構造登録者

Ojala, J.R.M.,Pikkarainen, T.,Tuuttila, A.,Sandalova, T.,Tryggvason, K. (登録日: 2007-02-21, 公開日: 2007-04-17, 最終更新日: 2024-11-13)

主引用文献

Ojala, J.R.,Pikkarainen, T.,Tuuttila, A.,Sandalova, T.,Tryggvason, K.
Crystal structure of the cysteine-rich domain of scavenger receptor MARCO reveals the presence of a basic and an acidic cluster that both contribute to ligand recognition.
J.Biol.Chem., 282:16654-16666, 2007

PubMed Abstract: MARCO is a trimeric class A scavenger receptor of macrophages and dendritic cells that recognizes polyanionic particles and pathogens. The distal, scavenger receptor cysteine-rich (SRCR) domain of the extracellular part of this receptor has been implicated in ligand binding. To provide a structural basis for understanding the ligand-binding mechanisms of MARCO, we have determined the crystal structure of the mouse MARCO SRCR domain. The recombinant SRCR domain purified as monomeric and dimeric forms, and their structures were determined at 1.78 and 1.77 A resolution, respectively. The monomer has a compact globular fold with a twisted five-stranded antiparallel beta-sheet and a long loop covering a single alpha-helix, whereas the dimer is formed via beta-strand swapping of two monomers, thus containing a large eight-stranded beta-sheet. Calculation of the surface electrostatic potential revealed that the beta-sheet region with several arginines forms a basic cluster. Unexpectedly, an acidic cluster was found in the long loop region. In the monomer, the acidic cluster is involved in metal ion binding. Studies with cells expressing various SRCR domain mutants showed that all of the arginines of the basic cluster are involved in ligand binding, suggesting a cooperative binding mechanism. Ligand binding is also dependent on the acidic cluster and Ca2+ ions whose depletion appears to affect ligand binding at least by modulating the electrostatic potential or relative domain orientation. We propose that the SRCR domain dimerization can contribute to the recognition of large ligands by providing a means for the MARCO receptor oligomerization.

PubMed: 17405873
DOI: 10.1074/jbc.M701750200

実験手法

X-RAY DIFFRACTION (1.77 Å)