Structural highlights
Function[TACY_CLOPE] Sulfhydryl-activated toxin that causes cytolysis by forming pores in cholesterol containing host membranes. After binding to target membranes, the protein assembles into a pre-pore complex. A conformation change leads to insertion in the host membrane and formation of an oligomeric pore complex. Cholesterol may be required for binding to host cell membranes, membrane insertion and pore formation. Can be reversibly inactivated by oxidation.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. Structural basis of pore formation by the bacterial toxin pneumolysin.,Tilley SJ, Orlova EV, Gilbert RJ, Andrew PW, Saibil HR Cell. 2005 Apr 22;121(2):247-56. PMID:15851031[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||
This page was last modified 06:29, 19 April 2017.