DOI: 10.1038/ncomms11293. Cryo-EM structure of lysenin pore elucidates membrane insertion by an aerolysin family protein

Cryo-EM structure of lysenin pore elucidates membrane insertion by an aerolysin family protein

10.1038/ncomms11293

Crossref journal-article

Springer Science and Business Media LLC

Nature Communications (297)

Abstract

AbstractLysenin from the coelomic fluid of the earthworm Eisenia fetida belongs to the aerolysin family of small β-pore-forming toxins (β-PFTs), some members of which are pathogenic to humans and animals. Despite efforts, a high-resolution structure of a channel for this family of proteins has been elusive and therefore the mechanism of activation and membrane insertion remains unclear. Here we determine the pore structure of lysenin by single particle cryo-EM, to 3.1 Å resolution. The nonameric assembly reveals a long β-barrel channel spanning the length of the complex that, unexpectedly, includes the two pre-insertion strands flanking the hypothetical membrane-insertion loop. Examination of other members of the aerolysin family reveals high structural preservation in this region, indicating that the membrane-insertion pathway in this family is conserved. For some toxins, proteolytic activation and pro-peptide removal will facilitate unfolding of the pre-insertion strands, allowing them to form the β-barrel of the channel.

Bibliography

Bokori-Brown, M., Martin, T. G., Naylor, C. E., Basak, A. K., Titball, R. W., & Savva, C. G. (2016). Cryo-EM structure of lysenin pore elucidates membrane insertion by an aerolysin family protein. Nature Communications, 7(1).

Authors 6

Monika Bokori-Brown (first)
Thomas G. Martin (additional)
Claire E. Naylor (additional)
Ajit K. Basak (additional)
Richard W. Titball (additional)
Christos G. Savva (additional)

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Dates

Type	When
Created	9 years, 4 months ago (April 6, 2016, 5:36 a.m.)
Deposited	2 years, 7 months ago (Jan. 4, 2023, 6:29 a.m.)
Indexed	3 weeks, 6 days ago (Aug. 6, 2025, 8:09 a.m.)
Issued	9 years, 4 months ago (April 6, 2016)
Published	9 years, 4 months ago (April 6, 2016)
Published Online	9 years, 4 months ago (April 6, 2016)

Funders 0

None

BibTeX

@article{Bokori_Brown_2016, title={Cryo-EM structure of lysenin pore elucidates membrane insertion by an aerolysin family protein}, volume={7}, ISSN={2041-1723}, url={http://dx.doi.org/10.1038/ncomms11293}, DOI={10.1038/ncomms11293}, number={1}, journal={Nature Communications}, publisher={Springer Science and Business Media LLC}, author={Bokori-Brown, Monika and Martin, Thomas G. and Naylor, Claire E. and Basak, Ajit K. and Titball, Richard W. and Savva, Christos G.}, year={2016}, month=apr }

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  "abstract": "<jats:title>Abstract</jats:title><jats:p>Lysenin from the coelomic fluid of the earthworm <jats:italic>Eisenia fetida</jats:italic> belongs to the aerolysin family of small \u03b2-pore-forming toxins (\u03b2-PFTs), some members of which are pathogenic to humans and animals. Despite efforts, a high-resolution structure of a channel for this family of proteins has been elusive and therefore the mechanism of activation and membrane insertion remains unclear. Here we determine the pore structure of lysenin by single particle cryo-EM, to 3.1\u2009\u00c5 resolution. The nonameric assembly reveals a long \u03b2-barrel channel spanning the length of the complex that, unexpectedly, includes the two pre-insertion strands flanking the hypothetical membrane-insertion loop. Examination of other members of the aerolysin family reveals high structural preservation in this region, indicating that the membrane-insertion pathway in this family is conserved. For some toxins, proteolytic activation and pro-peptide removal will facilitate unfolding of the pre-insertion strands, allowing them to form the \u03b2-barrel of the channel.</jats:p>",
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