2RD7

Human Complement Membrane Attack Proteins Share a Common Fold with Bacterial Cytolysins

2RD7 の概要

• エントリーDOI: 10.2210/pdb2rd7/pdb
• 分子名称: Complement component C8 alpha chain, Complement component C8 gamma chain, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: membrane attack system, cleavage on pair of basic residues, complement alternate pathway, complement pathway, cytolysis, egf-like domain, glycoprotein, immune response, innate immunity, membrane attack complex, polymorphism, secreted, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted: P07357 P07360
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 62281.59

構造登録者

Slade, D.J.,Lovelace, L.L.,Chruszcz, M.,Minor, W.,Lebioda, L.,Sodetz, J.M. (登録日: 2007-09-21, 公開日: 2008-05-27, 最終更新日: 2024-10-30)

主引用文献

Lovelace, L.L.,Cooper, C.L.,Sodetz, J.M.,Lebioda, L.
Structure of human C8 protein provides mechanistic insight into membrane pore formation by complement.
J. Biol. Chem., 286:17585-17592, 2011

PubMed Abstract: C8 is one of five complement proteins that assemble on bacterial membranes to form the lethal pore-like "membrane attack complex" (MAC) of complement. The MAC consists of one C5b, C6, C7, and C8 and 12-18 molecules of C9. C8 is composed of three genetically distinct subunits, C8α, C8β, and C8γ. The C6, C7, C8α, C8β, and C9 proteins are homologous and together comprise the MAC family of proteins. All contain N- and C-terminal modules and a central 40-kDa membrane attack complex perforin (MACPF) domain that has a key role in forming the MAC pore. Here, we report the 2.5 Å resolution crystal structure of human C8 purified from blood. This is the first structure of a MAC family member and of a human MACPF-containing protein. The structure shows the modules in C8α and C8β are located on the periphery of C8 and not likely to interact with the target membrane. The C8γ subunit, a member of the lipocalin family of proteins that bind and transport small lipophilic molecules, shows no occupancy of its putative ligand-binding site. C8α and C8β are related by a rotation of ∼22° with only a small translational component along the rotation axis. Evolutionary arguments suggest the geometry of binding between these two subunits is similar to the arrangement of C9 molecules within the MAC pore. This leads to a model of the MAC that explains how C8-C9 and C9-C9 interactions could facilitate refolding and insertion of putative MACPF transmembrane β-hairpins to form a circular pore.

PubMed: 21454577
DOI: 10.1074/jbc.M111.219766

実験手法

X-RAY DIFFRACTION (2.15 Å)