TY  - JOUR
A1  - Pee, Katharina van
A1  - Neuhaus, Alexander
A1  - D'Imprima, Edoardo
A1  - Mills, Deryck J.
A1  - Kühlbrandt, Werner
A1  - Yildiz, Özkan
T1  - CryoEM structures of membrane pore and prepore complex reveal cytolytic mechanism of Pneumolysin
T2  - eLife
N2  - Many pathogenic bacteria produce pore-forming toxins to attack and kill human cells. We have determined the 4.5 Å structure of the ~2.2 MDa pore complex of pneumolysin, the main virulence factor of Streptococcus pneumoniae, by cryoEM. The pneumolysin pore is a 400 Å ring of 42 membrane-inserted monomers. Domain 3 of the soluble toxin refolds into two ~85 Å β-hairpins that traverse the lipid bilayer and assemble into a 168-strand β-barrel. The pore complex is stabilized by salt bridges between β-hairpins of adjacent subunits and an internal α-barrel. The apolar outer barrel surface with large sidechains is immersed in the lipid bilayer, while the inner barrel surface is highly charged. Comparison of the cryoEM pore complex to the prepore structure obtained by electron cryo-tomography and the x-ray structure of the soluble form reveals the detailed mechanisms by which the toxin monomers insert into the lipid bilayer to perforate the target membrane.
KW  - Research article
KW  - biophysics and structural biology
KW  - microbiology and infectious disease
KW  - cholesterol-dependent cytolysin (cdc)
KW  - membrane pore
KW  - pore-forming toxin
KW  - electron cryo-microscopy (cryoem)
KW  - electron cryo-tomography (cryoet)
KW  - x-ray crystallography
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/45645
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-456457
SN  - 2050-084X
N1  - Copyright van Pee et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
VL  - 6
IS  - e23644
SP  - 1
EP  - 22
PB  - eLife Sciences Publications
CY  - Cambridge
ER  -