PDBsum entry 2qqh

Immune system, membrane protein

PDB id: 2qqh

Contents

Protein chain

304 a.a. *

Ligands

SO4 ×3

Metals

_NI

Waters ×44

* Residue conservation analysis

PDB id:

2qqh

Name:

Immune system, membrane protein

Title:

Structure of c8a-macpf reveals mechanism of membrane attack in complement immune defense

Structure:

Complement component c8 alpha chain. Chain: a. Synonym: complement component 8 subunit alpha. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: c8a. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.50Å R-factor: 0.256 R-free: 0.287

Authors:

M.A.Hadders,P.Gros

Key ref:

M.A.Hadders et al. (2007). Structure of C8alpha-MACPF reveals mechanism of membrane attack in complement immune defense. Science, 317, 1552-1554. PubMed id: 17872444 DOI: 10.1126/science.1147103

Date:

26-Jul-07 Release date: 25-Sep-07

Protein chain

P07357  (CO8A_HUMAN) -  Complement component C8 alpha chain from Homo sapiens

Seq: 584 a.a.

Struc: 304 a.a.*

* PDB and UniProt seqs differ at 14 residue positions (black crosses)

DOI no: 10.1126/science.1147103

Science 317:1552-1554 (2007)

PubMed id: 17872444

Structure of C8alpha-MACPF reveals mechanism of membrane attack in complement immune defense.

M.A.Hadders, D.X.Beringer, P.Gros.

ABSTRACT

Membrane attack is important for mammalian immune defense against invading microorganisms and infected host cells. Proteins of the complement membrane attack complex (MAC) and the protein perforin share a common MACPF domain that is responsible for membrane insertion and pore formation. We determined the crystal structure of the MACPF domain of complement component C8alpha at 2.5 angstrom resolution and show that it is structurally homologous to the bacterial, pore-forming, cholesterol-dependent cytolysins. The structure displays two regions that (in the bacterial cytolysins) refold into transmembrane beta hairpins, forming the lining of a barrel pore. Local hydrophobicity explains why C8alpha is the first complement protein to insert into the membrane. The size of the MACPF domain is consistent with known C9 pore sizes. These data imply that these mammalian and bacterial cytolytic proteins share a common mechanism of membrane insertion.

Selected figure(s)

Figure 1.
Fig. 1. Structure of human C8 -MACPF. C representation of C8 -MACPF (A) and intermedilysin (PDB accession code 1s3r) (B) in two views. The top and bottom halves of the molecule are denoted d1 (blue) and d3 (brown), respectively. The central kinked ß sheet (part of both d1 and d3) is shown in green. The additional domains d2 and d4 in intermedilysin are shown in gray. Figures are produced with PyMOL (30).

Figure 2.
Fig. 2. Comparison of putative transmembrane regions. (A) Cartoon diagrams of domains d3 of C8 -MACPF (left) and intermedilysin (right). The putative ß hairpin regions ß1-ß2 and TMH1 are colored in dark brown, and ß3-ß4 and TMH2 are colored in light brown. (B) Sequence alignment of (i) the ß1-ß2 and ß3-ß4 regions of C8 , C9, and perforin (Perf) and (ii) TMH1 and TMH2 of perfringolysin (PFO) and intermedilysin (ILY). Residues (31) are colored according to character: hydrophobic (green), positively charged (blue), negatively charged (red), and hydrophilic (white). Yellow indicates cysteine residues. Secondary structure elements, as observed for C8 -MACPF and intermedilysin, are indicated. Putative transmembrane regions are indicated by gray boxes.

The above figures are reprinted by permission from the AAAs: Science (2007, 317, 1552-1554) copyright 2007.

Figures were selected by the author.