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bioRxiv · 10.64898/2026.10.30.762977

Substrate-induced asymmetry coordinates lipoprotein handover and abaucin trapping in Acinetobacter baumannii LolDF

Kong, J.·Zhu, Z.·Lin, Z.·Yao, N.·Ye, H.·Gu, H.·He, R.·Chen, M.·Lu, M.·Sun, H.·Xiao, Y.·Li, Z.
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Abstract

The homodimeric lipoprotein transporter LolDF supports outer-membrane biogenesis in Acinetobacter baumannii. How homodimeric LolDF generates directional lipoprotein transport, and how the reported two- and four-abaucin states are related, remain unclear. Using defined lipidated AbLolB and AbLolA, we show that substrate binding breaks LolF symmetry: LolFB primarily accommodates the lipid anchor, LolFA positions the adjacent polypeptide, and LolA docks asymmetrically through the LolF hook and an AbLolA-specific loop. C1 reconstruction of the wide abaucin state reveals non-equivalent central ligands, whereas C2 processing of the same particles averages this asymmetry; the two peripheral ligands form a stable inhibitory core, while the central sites are conditionally occupied in the expanded cavity. Abaucin inhibits ATPase activity and LolA-mediated transfer from substrate-associated LolDF, supporting a unified mechanism in which substrate-induced asymmetry organizes productive handover and its conformational plasticity is redirected during inhibition.

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Kong, J., Zhu, Z., Lin, Z., Yao, N., Ye, H., Gu, H., He, R., Chen, M., Lu, M., Sun, H., Xiao, Y., Li, Z.. 2026-11-02. Substrate-induced asymmetry coordinates lipoprotein handover and abaucin trapping in Acinetobacter baumannii LolDF. https://doi.org/10.64898/2026.10.30.762977

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