2MPM

Structural Basis of Receptor Sulfotyrosine Recognition by a CC Chemokine: the N-terminal Region of CCR3 Bound to CCL11/Eotaxin-1

2MPM の概要

• エントリーDOI: 10.2210/pdb2mpm/pdb
• 関連するPDBエントリー: 1EOT 2EOT
• NMR情報: BMRB: 19989
• 分子名称: Eotaxin, CCR3 (2 entities in total)
• 機能のキーワード: chemokine ccl11, chemokine receptor ccr3, sulfopeptide, cytokine
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted: P51671
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 10320.96

構造登録者

Millard, C.J.,Ludeman, J.P.,Canals, M.,Bridgford, J.L.,Hinds, M.G.,Clayton, D.J.,Christopoulos, A.,Payne, R.J.,Stone, M.J. (登録日: 2014-05-26, 公開日: 2014-12-10, 最終更新日: 2024-11-06)

主引用文献

Millard, C.J.,Ludeman, J.P.,Canals, M.,Bridgford, J.L.,Hinds, M.G.,Clayton, D.J.,Christopoulos, A.,Payne, R.J.,Stone, M.J.
Structural Basis of Receptor Sulfotyrosine Recognition by a CC Chemokine: The N-Terminal Region of CCR3 Bound to CCL11/Eotaxin-1.
Structure, 22:1571-1581, 2014

PubMed Abstract: Trafficking of leukocytes in immune surveillance and inflammatory responses is activated by chemokines engaging their receptors. Sulfation of tyrosine residues in peptides derived from the eosinophil chemokine receptor CCR3 dramatically enhances binding to cognate chemokines. We report the structural basis of this recognition and affinity enhancement. We describe the structure of a CC chemokine (CCL11/eotaxin-1) bound to a fragment of a chemokine receptor: residues 8–23 of CCR3, including two sulfotyrosine residues. We also show that intact CCR3 is sulfated and sulfation enhances receptor activity. The CCR3 sulfotyrosine residues form hydrophobic, salt bridge and cation-p interactions with residues that are highly conserved in CC chemokines. However, the orientation of the chemokine relative to the receptor N terminus differs substantially from those observed for two CXC chemokines, suggesting that initial binding of the receptor sulfotyrosine residues guides subsequent steps in receptor activation, thereby influencing the receptor conformational changes and signaling.

PubMed: 25450766
DOI: 10.1016/j.str.2014.08.023

実験手法

SOLUTION NMR