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. 2022 Sep 7;609(7927):582–589. doi: 10.1038/s41586-022-05181-3

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Extended Data Fig. 8 — a, Model of Paraprevotella-mediated trypsin degradation: 00502 and 00509 proteins are transported across the outer membrane of Paraprevotella via the Type IX secretion system (T9SS). PorU is an essential T9SS component that cleaves the C-terminal domain (CTD) of T9SS-dependent proteins and anchors the proteins to Paraprevotella LPS molecules. WecA mediates the initial step of LPS O-glycan synthesis, and disruption of WecA function (e.g., with tunicamycin treatment) causes release of T9SS-dependent proteins. 00502 acts as a core effector component, facilitating trypsin association and auto-degradation possibly mediated by 00502 oligomerization, whereas 00509 may play a supporting and dispensable role in facilitating trypsin recruitment. Sec: Sec system that exports proteins across the cytoplasmic membrane. b, AlphaFold2-based structural prediction of P. clara 00502 protein with individual domains highlighted. Four out of the five Ig-like domains are shown; the last Ig-like domain that serves as the T9SS C-terminal target domain therefore does not form part of the Ig-like domain clustering zone is omitted here (shown separately in panel g). c–f, AlphaFold2-based structural prediction of P. xylaniphila, P. rara, P. rodentium and P. muris 00502 homologues with the conserved Ig-like domain clustering zone highlighted. g, Alignment of the C-terminal domain (CTD) of P. clara 00502 with that of Porphyromonas gingivalis RgpB protein. The “KXXXK” motif is a signature of T9SS C-terminal target domain-containing proteins.