5aoe
From Proteopedia
Crystal structure of pneumolysin D168A mutant.
Structural highlights
Function[TACY_STRP2] Sulfhydryl-activated toxin that causes cytolysis by forming pores in cholesterol containing host membranes. After binding to target membranes, the protein undergoes a major conformation change, leading to its insertion in the host membrane and formation of an oligomeric pore complex. Cholesterol may be required for binding to host membranes, membrane insertion and pore formation. Can be reversibly inactivated by oxidation (By similarity). Publication Abstract from PubMedMany pathogenic bacteria produce pore-forming toxins to attack and kill human cells. We have determined the 4.5 A 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 A ring of 42 membrane-inserted monomers. Domain D3 of the soluble toxin refolds into two ~85 A beta-hairpins that traverse the lipid bilayer and assemble into a 168-strand beta-barrel. The pore complex is stabilized by salt bridges between beta-hairpins of adjacent subunits and an internal alpha-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. CryoEM structures of membrane pore and prepore complex reveal cytolytic mechanism of Pneumolysin.,van Pee K, Neuhaus A, D'Imprima E, Mills DJ, Kuhlbrandt W, Yildiz O Elife. 2017 Mar 21;6. pii: e23644. doi: 10.7554/eLife.23644. PMID:28323617[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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