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Cited by 1Legionella and Acanthamoeba researchCellular Mechanics and InteractionsMicrotubule and mitosis dynamics

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Cryo-EM structure revealed a novel F-actin binding motif in a Legionella pneumophila lysine fatty acyltransferase

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Zeng, Wenjie W, Komaniecki, Garrison, Liu, Jiaze, Lin, Hening, Mao, Yuxin·2026·eLife
DOI 10.7554/elife.106975PMC PMC12851578

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Abstract

Legionella pneumophila is an opportunistic bacterial pathogen that causes Legionnaires’ disease. To establish an intracellular niche conducive to replication, L. pneumophila translocates a diverse array of effector proteins that manipulate various host cellular processes, including the actin cytoskeleton. In a screen for effectors that alter actin dynamics, we identified a Legionella effector, Lfat1 (lpg1387), which colocalizes with the actin cytoskeleton in eukaryotic cells. Lfat1 specifically binds F-actin through a novel actin-binding domain (ABD). High-resolution cryo-electron microscopy (Cryo-EM) analysis revealed that this ABD forms a long α-helix hairpin, with its tip interacting with subdomains I and II of two adjacent actin molecules within the F-actin filament. Interestingly, while individual α-helices of the hairpin fail to bind F-actin, co-expression as separate fusion proteins restores binding activity. Furthermore, we demonstrated that Lfat1 exhibits lysine fatty acyltransferase (KFAT) activity, targeting host small GTPases. These findings establish a foundation for studying the KFAT family of bacterial toxins and uncover a novel F-actin-binding motif, providing an alternative F-actin marker with notable flexibility.

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Metadata

Authors
Zeng, W. W., Komaniecki, G., Liu, J., Lin, H., & Mao, Y.
Affiliations
  • Cornell University (US)
  • University of Wisconsin–Parkside (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Mao, Yuxin
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2026-01-28
Volume
14
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.106975
PMC
PMC12851578
OpenAlex
W4411370551
Cited by
1
References
2
Citations by year
2026: 1
Type
posted content
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • University of Chicago (cc-by)
Funders
  • National Institutes of Health (T32, R01GM144452, R01AI153110)
  • Cornell University (the Sadov Graduate Student Fellowship)
  • Howard Hughes Medical Institute
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Legionella and Acanthamoeba research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
Keywords
Legionella pneumophila, actin-binding domain, bacterial effector proteins, bacterial toxins, Legionnaires' disease
MeSH terms
Actins, Acyltransferases, Bacterial Proteins, Humans, Models, Molecular, Protein Binding, Legionella pneumophila, Cryoelectron Microscopy, Amino Acid Motifs

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