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PDBsum entry 2bk2
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Contents |
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* Residue conservation analysis
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* C-alpha coords only
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DOI no:
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Cell
121:247-256
(2005)
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PubMed id:
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Structural basis of pore formation by the bacterial toxin pneumolysin.
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S.J.Tilley,
E.V.Orlova,
R.J.Gilbert,
P.W.Andrew,
H.R.Saibil.
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ABSTRACT
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The bacterial toxin pneumolysin is released as a soluble monomer that kills
target cells by assembling into large oligomeric rings and forming pores in
cholesterol-containing membranes. Using cryo-EM and image processing, we have
determined the structures of membrane-surface bound (prepore) and inserted-pore
oligomer forms, providing a direct observation of the conformational transition
into the pore form of a cholesterol-dependent cytolysin. In the pore structure,
the domains of the monomer separate and double over into an arch, forming a wall
sealing the bilayer around the pore. This transformation is accomplished by
substantial refolding of two of the four protein domains along with deformation
of the membrane. Extension of protein density into the bilayer supports earlier
predictions that the protein inserts beta hairpins into the membrane. With an
oligomer size of up to 44 subunits in the pore, this assembly creates a
transmembrane channel 260 A in diameter lined by 176 beta strands.
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Selected figure(s)
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Figure 2.
Figure 2. 3D Reconstructions of Prepore and Pore Forms of
Pneumolysin
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Figure 4.
Figure 4. Atomic Structure Fits of Prepore and Pore
Structures
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The above figures are
reprinted
by permission from Cell Press:
Cell
(2005,
121,
247-256)
copyright 2005.
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Figures were
selected
by the author.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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H.Shimada,
and
S.Kitada
(2011).
Mega assemblages of oligomeric aerolysin-like toxins stabilized by toxin-associating membrane proteins.
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J Biochem,
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J.Frauenfeld,
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(2011).
Cryo-EM structure of the ribosome-SecYE complex in the membrane environment.
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Nat Struct Mol Biol,
18,
614-621.
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PDB codes:
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S.Okumura,
H.Saitoh,
T.Ishikawa,
K.Inouye,
and
E.Mizuki
(2011).
Mode of action of parasporin-4, a cytocidal protein from Bacillus thuringiensis.
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Biochim Biophys Acta,
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T.G.Popova,
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Anthrolysin O and fermentation products mediate the toxicity of Bacillus anthracis to lung epithelial cells under microaerobic conditions.
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FEMS Immunol Med Microbiol,
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Human perforin employs different avenues to damage membranes.
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H.R.Saibil,
and
J.C.Whisstock
(2010).
The structural basis for membrane binding and pore formation by lymphocyte perforin.
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Nature,
468,
447-451.
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PDB code:
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S.C.Kondos,
T.Hatfaludi,
I.Voskoboinik,
J.A.Trapani,
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Tissue Antigens,
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S.W.Tait,
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Mitochondria and cell death: outer membrane permeabilization and beyond.
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Nat Rev Mol Cell Biol,
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V.I.Pushkareva,
and
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(2010).
Listeria monocytogenes virulence factor Listeriolysin O favors bacterial growth in co-culture with the ciliate Tetrahymena pyriformis, causes protozoan encystment and promotes bacterial survival inside cysts.
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BMC Microbiol,
10,
26.
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W.R.Hesse,
K.J.Freedman,
D.K.Yi,
C.W.Ahn,
and
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(2010).
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Small,
6,
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A.I.Iliev,
J.R.Djannatian,
F.Opazo,
J.Gerber,
R.Nau,
T.J.Mitchell,
and
F.S.Wouters
(2009).
Rapid microtubule bundling and stabilization by the Streptococcus pneumoniae neurotoxin pneumolysin in a cholesterol-dependent, non-lytic and Src-kinase dependent manner inhibits intracellular trafficking.
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Mol Microbiol,
71,
461-477.
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B.Schafer,
J.Quispe,
V.Choudhary,
J.E.Chipuk,
T.G.Ajero,
H.Du,
R.Schneiter,
and
T.Kuwana
(2009).
Mitochondrial outer membrane proteins assist Bid in Bax-mediated lipidic pore formation.
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Mol Biol Cell,
20,
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J.J.Flanagan,
R.K.Tweten,
A.E.Johnson,
and
A.P.Heuck
(2009).
Cholesterol exposure at the membrane surface is necessary and sufficient to trigger perfringolysin O binding.
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Biochemistry,
48,
3977-3987.
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M.C.Dessing,
R.A.Hirst,
A.F.de Vos,
and
T.van der Poll
(2009).
Role of Toll-like receptors 2 and 4 in pulmonary inflammation and injury induced by pneumolysin in mice.
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PLoS One,
4,
e7993.
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M.Mueller,
U.Grauschopf,
T.Maier,
R.Glockshuber,
and
N.Ban
(2009).
The structure of a cytolytic alpha-helical toxin pore reveals its assembly mechanism.
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Nature,
459,
726-730.
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PDB code:
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R.W.Bourdeau,
E.Malito,
A.Chenal,
B.L.Bishop,
M.W.Musch,
M.L.Villereal,
E.B.Chang,
E.M.Mosser,
R.F.Rest,
and
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(2009).
Cellular Functions and X-ray Structure of Anthrolysin O, a Cholesterol-dependent Cytolysin Secreted by Bacillus anthracis.
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J Biol Chem,
284,
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PDB code:
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S.Lachapelle,
R.K.Tweten,
and
E.M.Hotze
(2009).
Intermedilysin-Receptor Interactions during Assembly of the Pore Complex: ASSEMBLY INTERMEDIATES INCREASE HOST CELL SUSCEPTIBILITY TO COMPLEMENT-MEDIATED LYSIS.
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J Biol Chem,
284,
12719-12726.
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Y.Cheng,
and
T.Walz
(2009).
The advent of near-atomic resolution in single-particle electron microscopy.
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Annu Rev Biochem,
78,
723-742.
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Y.S.Liu,
Y.Fang,
and
K.Ramani
(2009).
Using least median of squares for structural superposition of flexible proteins.
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BMC Bioinformatics,
10,
29.
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A.Kadioglu,
J.N.Weiser,
J.C.Paton,
and
P.W.Andrew
(2008).
The role of Streptococcus pneumoniae virulence factors in host respiratory colonization and disease.
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Nat Rev Microbiol,
6,
288-301.
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C.G.Savva,
J.S.Dewey,
J.Deaton,
R.L.White,
D.K.Struck,
A.Holzenburg,
and
R.Young
(2008).
The holin of bacteriophage lambda forms rings with large diameter.
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Mol Microbiol,
69,
784-793.
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C.J.Rosado,
S.Kondos,
T.E.Bull,
M.J.Kuiper,
R.H.Law,
A.M.Buckle,
I.Voskoboinik,
P.I.Bird,
J.A.Trapani,
J.C.Whisstock,
and
M.A.Dunstone
(2008).
The MACPF/CDC family of pore-forming toxins.
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Cell Microbiol,
10,
1765-1774.
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C.L.Lawson,
S.Dutta,
J.D.Westbrook,
K.Henrick,
and
H.M.Berman
(2008).
Representation of viruses in the remediated PDB archive.
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Acta Crystallogr D Biol Crystallogr,
64,
874-882.
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F.C.Kurschus,
E.Fellows,
E.Stegmann,
and
D.E.Jenne
(2008).
Granzyme B delivery via perforin is restricted by size, but not by heparan sulfate-dependent endocytosis.
|
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Proc Natl Acad Sci U S A,
105,
13799-13804.
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G.Anderluh,
and
J.H.Lakey
(2008).
Disparate proteins use similar architectures to damage membranes.
|
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Trends Biochem Sci,
33,
482-490.
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J.A.Preston,
and
D.H.Dockrell
(2008).
Virulence factors in pneumococcal respiratory pathogenesis.
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Future Microbiol,
3,
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K.Shahidullah,
and
E.London
(2008).
Effect of lipid composition on the topography of membrane-associated hydrophobic helices: stabilization of transmembrane topography by anionic lipids.
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J Mol Biol,
379,
704-718.
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M.Krupovic,
and
D.H.Bamford
(2008).
Holin of bacteriophage lambda: structural insights into a membrane lesion.
|
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Mol Microbiol,
69,
781-783.
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A.I.Iliev,
J.R.Djannatian,
R.Nau,
T.J.Mitchell,
and
F.S.Wouters
(2007).
Cholesterol-dependent actin remodeling via RhoA and Rac1 activation by the Streptococcus pneumoniae toxin pneumolysin.
|
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Proc Natl Acad Sci U S A,
104,
2897-2902.
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C.E.Soltani,
E.M.Hotze,
A.E.Johnson,
and
R.K.Tweten
(2007).
Specific protein-membrane contacts are required for prepore and pore assembly by a cholesterol-dependent cytolysin.
|
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J Biol Chem,
282,
15709-15716.
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C.J.Rosado,
A.M.Buckle,
R.H.Law,
R.E.Butcher,
W.T.Kan,
C.H.Bird,
K.Ung,
K.A.Browne,
K.Baran,
T.A.Bashtannyk-Puhalovich,
N.G.Faux,
W.Wong,
C.J.Porter,
R.N.Pike,
A.M.Ellisdon,
M.C.Pearce,
S.P.Bottomley,
J.Emsley,
A.I.Smith,
J.Rossjohn,
E.L.Hartland,
I.Voskoboinik,
J.A.Trapani,
P.I.Bird,
M.A.Dunstone,
and
J.C.Whisstock
(2007).
A common fold mediates vertebrate defense and bacterial attack.
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Science,
317,
1548-1551.
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PDB code:
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M.A.Hadders,
D.X.Beringer,
and
P.Gros
(2007).
Structure of C8alpha-MACPF reveals mechanism of membrane attack in complement immune defense.
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Science,
317,
1552-1554.
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PDB code:
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S.K.Das,
M.Darshi,
S.Cheley,
M.I.Wallace,
and
H.Bayley
(2007).
Membrane protein stoichiometry determined from the step-wise photobleaching of dye-labelled subunits.
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Chembiochem,
8,
994-999.
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S.Meier,
and
S.Ozbek
(2007).
A biological cosmos of parallel universes: does protein structural plasticity facilitate evolution?
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Bioessays,
29,
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H.M.Berman,
S.K.Burley,
W.Chiu,
A.Sali,
A.Adzhubei,
P.E.Bourne,
S.H.Bryant,
R.L.Dunbrack,
K.Fidelis,
J.Frank,
A.Godzik,
K.Henrick,
A.Joachimiak,
B.Heymann,
D.Jones,
J.L.Markley,
J.Moult,
G.T.Montelione,
C.Orengo,
M.G.Rossmann,
B.Rost,
H.Saibil,
T.Schwede,
D.M.Standley,
and
J.D.Westbrook
(2006).
Outcome of a workshop on archiving structural models of biological macromolecules.
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Structure,
14,
1211-1217.
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J.Banerjee,
J.Singh,
M.C.Joshi,
S.Ghosh,
and
N.Banerjee
(2006).
The cytotoxic fimbrial structural subunit of Xenorhabdus nematophila is a pore-forming toxin.
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J Bacteriol,
188,
7957-7962.
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J.Pizarro-Cerdá,
and
P.Cossart
(2006).
Subversion of cellular functions by Listeria monocytogenes.
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J Pathol,
208,
215-223.
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L.Jayasinghe,
G.Miles,
and
H.Bayley
(2006).
Role of the amino latch of staphylococcal alpha-hemolysin in pore formation: a co-operative interaction between the N terminus and position 217.
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J Biol Chem,
281,
2195-2204.
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M.Desvaux,
M.Hébraud,
I.R.Henderson,
and
M.J.Pallen
(2006).
Type III secretion: what's in a name?
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Trends Microbiol,
14,
157-160.
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N.Eifler,
M.Vetsch,
M.Gregorini,
P.Ringler,
M.Chami,
A.Philippsen,
A.Fritz,
S.A.Müller,
R.Glockshuber,
A.Engel,
and
U.Grauschopf
(2006).
Cytotoxin ClyA from Escherichia coli assembles to a 13-meric pore independent of its redox-state.
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EMBO J,
25,
2652-2661.
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P.Grob,
M.J.Cruse,
C.Inouye,
M.Peris,
P.A.Penczek,
R.Tjian,
and
E.Nogales
(2006).
Cryo-electron microscopy studies of human TFIID: conformational breathing in the integration of gene regulatory cues.
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Structure,
14,
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S.B.Tzokov,
N.R.Wyborn,
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(2006).
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J Biol Chem,
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(2006).
Real-time monitoring of the membrane-binding and insertion properties of the cholesterol-dependent cytolysin anthrolysin O from Bacillus anthracis.
|
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J Mol Recognit,
19,
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S.J.Tilley,
and
H.R.Saibil
(2006).
The mechanism of pore formation by bacterial toxins.
|
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Curr Opin Struct Biol,
16,
230-236.
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S.Kayal,
and
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(2006).
Listeriolysin O: a key protein of Listeria monocytogenes with multiple functions.
|
| |
FEMS Microbiol Rev,
30,
514-529.
|
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S.Kitada,
Y.Abe,
H.Shimada,
Y.Kusaka,
Y.Matsuo,
H.Katayama,
S.Okumura,
T.Akao,
E.Mizuki,
O.Kuge,
Y.Sasaguri,
M.Ohba,
and
A.Ito
(2006).
Cytocidal actions of parasporin-2, an anti-tumor crystal toxin from Bacillus thuringiensis.
|
| |
J Biol Chem,
281,
26350-26360.
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A.E.Johnson
(2005).
Fluorescence approaches for determining protein conformations, interactions and mechanisms at membranes.
|
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Traffic,
6,
1078-1092.
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H.Bayley,
L.Jayasinghe,
and
M.Wallace
(2005).
Prepore for a breakthrough.
|
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Nat Struct Mol Biol,
12,
385-386.
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O.Llorca
(2005).
Introduction to 3D reconstruction of macromolecules using single particle electron microscopy.
|
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Acta Pharmacol Sin,
26,
1153-1164.
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R.J.Gilbert
(2005).
Inactivation and activity of cholesterol-dependent cytolysins: what structural studies tell us.
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Structure,
13,
1097-1106.
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R.K.Tweten
(2005).
Cholesterol-dependent cytolysins, a family of versatile pore-forming toxins.
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Infect Immun,
73,
6199-6209.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
