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PDBsum entry 2qqh
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Immune system, membrane protein
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PDB id
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2qqh
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References listed in PDB file
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Key reference
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Title
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Structure of c8alpha-Macpf reveals mechanism of membrane attack in complement immune defense.
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Authors
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M.A.Hadders,
D.X.Beringer,
P.Gros.
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Ref.
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Science, 2007,
317,
1552-1554.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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).
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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.
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The above figures are
reprinted
by permission from the AAAs:
Science
(2007,
317,
1552-1554)
copyright 2007.
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