2K3U

Structure of the tyrosine-sulfated C5a receptor N-terminus in complex with the immune evasion protein CHIPS.

2K3U の概要

• エントリーDOI: 10.2210/pdb2k3u/pdb
• 関連するPDBエントリー: 1XEE
• NMR情報: BMRB: 15778
• 分子名称: Chemotaxis inhibitory protein, C5a anaphylatoxin chemotactic receptor 1 (2 entities in total)
• 機能のキーワード: chemotaxis inhibitory protein (chips), sulfated tyrosine, gpcr membrane protein c5ar, anaphylotoxin c5a, staphylococcus aureus, complement cascade, secreted, virulence, immune system
• 由来する生物種: Staphylococcus aureus subsp. aureus str. Newman; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 13186.78

構造登録者

Ippel, J.H.,Bunschoten, A.,Kemmink, J.,Liskamp, R. (登録日: 2008-05-16, 公開日: 2009-03-10, 最終更新日: 2024-11-06)

主引用文献

Ippel, J.H.,de Haas, C.J.,Bunschoten, A.,van Strijp, J.A.,Kruijtzer, J.A.,Liskamp, R.M.,Kemmink, J.
Structure of the Tyrosine-sulfated C5a Receptor N Terminus in Complex with Chemotaxis Inhibitory Protein of Staphylococcus aureus.
J.Biol.Chem., 284:12363-12372, 2009

PubMed Abstract: Complement component C5a is a potent pro-inflammatory agent inducing chemotaxis of leukocytes toward sites of infection and injury. C5a mediates its effects via its G protein-coupled C5a receptor (C5aR). Although under normal conditions highly beneficial, excessive levels of C5a can be deleterious to the host and have been related to numerous inflammatory diseases. A natural inhibitor of the C5aR is chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS). CHIPS is a 121-residue protein excreted by S. aureus. It binds the N terminus of the C5aR (residues 1-35) with nanomolar affinity and thereby potently inhibits C5a-mediated responses in human leukocytes. Therefore, CHIPS provides a starting point for the development of new anti-inflammatory agents. Two O-sulfated tyrosine residues located at positions 11 and 14 within the C5aR N terminus play a critical role in recognition of C5a, but their role in CHIPS binding has not been established so far. By isothermal titration calorimetry, using synthetic Tyr-11- and Tyr-14-sulfated and non-sulfated C5aR N-terminal peptides, we demonstrate that the sulfate groups are essential for tight binding between the C5aR and CHIPS. In addition, the NMR structure of the complex of CHIPS and a sulfated C5aR N-terminal peptide reveals the precise binding motif as well as the distinct roles of sulfated tyrosine residues sY11 and sY14. These results provide a molecular framework for the design of novel CHIPS-based C5aR inhibitors.

PubMed: 19251703
DOI: 10.1074/jbc.M808179200

実験手法

SOLUTION NMR