4BIK

Structure of a disulfide locked mutant of Intermedilysin with human CD59

4BIK の概要

• エントリーDOI: 10.2210/pdb4bik/pdb
• 分子名称: INTERMEDILYSIN, CD59 GLYCOPROTEIN (2 entities in total)
• 機能のキーワード: complement, cholesterol dependent cytotoxin, immune system, membrane attack complex
• 由来する生物種: STREPTOCOCCUS INTERMEDIUS; 詳細
• 細胞内の位置: Cell membrane; Lipid-anchor, GPI-anchor: P13987
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 136522.69

構造登録者

Johnson, S.,Brooks, N.J.,Smith, R.A.G.,Lea, S.M.,Bubeck, D. (登録日: 2013-04-10, 公開日: 2013-05-08, 最終更新日: 2023-12-20)

主引用文献

Johnson, S.,Brooks, N.J.,Smith, R.A.G.,Lea, S.M.,Bubeck, D.
Structural Basis for Recognition of the Pore- Forming Toxin Intermedilysin by Human Complement Receptor Cd59
Cell Rep., 3:1369-, 2013

PubMed Abstract: Pore-forming proteins containing the structurally conserved membrane attack complex/perforin fold play an important role in immunity and host-pathogen interactions. Intermedilysin (ILY) is an archetypal member of a cholesterol-dependent cytolysin subclass that hijacks the complement receptor CD59 to make cytotoxic pores in human cells. ILY directly competes for the membrane attack complex binding site on CD59, rendering cells susceptible to complement lysis. To understand how these bacterial pores form in lipid bilayers and the role CD59 plays in complement regulation, we determined the crystal structure of human CD59 bound to ILY. Here, we show the ILY-CD59 complex at 3.5 Å resolution and identify two interfaces mediating this host-pathogen interaction. An ILY-derived peptide based on the binding site inhibits pore formation in a CD59-containing liposome model system. These data provide insight into how CD59 coordinates ILY monomers, nucleating an early prepore state, and suggest a potential mechanism of inhibition for the complement terminal pathway.

PubMed: 23665225
DOI: 10.1016/J.CELREP.2013.04.029

実験手法

X-RAY DIFFRACTION (3.494 Å)