6mrt
12-meric ClyA pore complex12-meric ClyA pore complex
Structural highlights
Function[HLYE_ECOLI] Toxin, which has some hemolytic activity towards mammalian cells. Acts by forming a pore-like structure upon contact with mammalian cells.[1] Publication Abstract from PubMedPore-forming proteins (PFPs) represent a functionally important protein family, that are found in organisms from viruses to humans. As a major branch of PFPs, bacteria pore-forming toxins (PFTs) permeabilize membranes and usually cause the death of target cells. E. coli hemolysin ClyA is the first member with the pore complex structure solved among alpha-PFTs, employing alpha-helices as transmembrane elements. ClyA is proposed to form pores composed of various numbers of protomers. With high-resolution cryo-EM structures, we observe that ClyA pore complexes can exist as newly confirmed oligomers of a tridecamer and a tetradecamer, at estimated resolutions of 3.2 A and 4.3 A, respectively. The 2.8 A cryo-EM structure of a dodecamer dramatically improves the existing structural model. Structural analysis indicates that protomers from distinct oligomers resemble each other and neighboring protomers adopt a conserved interaction mode. We also show a stabilized intermediate state of ClyA during the transition process from soluble monomers to pore complexes. Unexpectedly, even without the formation of mature pore complexes, ClyA can permeabilize membranes and allow leakage of particles less than ~400 Daltons. In addition, we are the first to show that ClyA forms pore complexes in the presence of cholesterol within artificial liposomes. These findings provide new mechanistic insights into the dynamic process of pore assembly for the prototypical alpha-PFT ClyA. High-resolution cryo-EM structures of the E. coli hemolysin ClyA oligomers.,Peng W, de Souza Santos M, Li Y, Tomchick DR, Orth K PLoS One. 2019 May 2;14(5):e0213423. doi: 10.1371/journal.pone.0213423., eCollection 2019. PMID:31048915[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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