Cyclization of archaeal membrane lipids impacts membrane protein activity and archaellum formation

Yang, Wei; Feng, Xi; Chen, Huahui; Liman, Geraldy Lie Stefanus; Santangelo, Thomas J.; Zhang, Changyi; Zeng, Zhirui

doi:10.1073/pnas.2423648122

Cyclization of archaeal membrane lipids impacts membrane protein activity and archaellum formation

Journal Article · Mon May 12 00:00:00 EDT 2025 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.2423648122· OSTI ID:2565534

; Feng, Xi; Chen, Huahui; ; ; Zhang, Changyi;

Enhancement of the cyclization of membrane lipids GDGTs (glycerol dialkyl glycerol tetraethers) is a critical strategy for archaea to adapt to various environmental stresses. However, the physiological function of membrane lipid cyclization remains unclear. Here, we reported that the GDGT ring synthases mutant, deficient in GDGT cyclization, inhibited archaellum formation and reduced cell motility in thermoacidophilic crenarchaeon Sulfolobus acidocaldarius . This inhibition was caused by decreased transcription of the archaellum operon, likely due to cleavage of the C-terminal domains in transmembrane proteins ArnRs, the transcription factors that regulate archaellum operon expression. The transcriptomic and proteomic analysis showed deficiency of GDGT cyclization broadly impacted the expression of membrane associate proteins, including respiratory chain proteins, and decreased cellular ATP concentration. Moreover, phylogenetic analysis demonstrated that the correlation between GDGT cyclization and archaellum formation is widespread among (hyper)thermophilic archaea, and this was further verified in the euryarchaeon Thermococcus kodakarensis. Our findings suggested that archaea modify their membrane lipids to profoundly alter cellular appendages and cell physiology to adapt to environmental fluctuations.

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Sponsoring Organization:: USDOE

Grant/Contract Number:: SC0014597

OSTI ID:: 2565534

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 20 Vol. 122; ISSN 0027-8424

Publisher:: Proceedings of the National Academy of SciencesCopyright Statement

Country of Publication:: United States

Language:: English

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