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-Structure paper
タイトル | Molecular basis of TMPRSS2 recognition by Paeniclostridium sordellii hemorrhagic toxin. |
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ジャーナル・号・ページ | Nat Commun, Vol. 15, Issue 1, Page 1976, Year 2024 |
掲載日 | 2024年3月4日 |
![]() | Ruoyu Zhou / Liuqing He / Jiahao Zhang / Xiaofeng Zhang / Yanyan Li / Xiechao Zhan / Liang Tao / ![]() |
PubMed 要旨 | Hemorrhagic toxin (TcsH) is a major virulence factor produced by Paeniclostridium sordellii, which is a non-negligible threat to women undergoing childbirth or abortions. Recently, Transmembrane ...Hemorrhagic toxin (TcsH) is a major virulence factor produced by Paeniclostridium sordellii, which is a non-negligible threat to women undergoing childbirth or abortions. Recently, Transmembrane Serine Protease 2 (TMPRSS2) was identified as a host receptor of TcsH. Here, we show the cryo-EM structures of the TcsH-TMPRSS2 complex and uncover that TcsH binds to the serine protease domain (SPD) of TMPRSS2 through the CROP unit-VI. This receptor binding mode is unique among LCTs. Five top surface loops of TMPRSS2, which also determine the protease substrate specificity, constitute the structural determinants recognized by TcsH. The binding of TcsH inhibits the proteolytic activity of TMPRSS2, whereas its implication in disease manifestations remains unclear. We further show that mutations selectively disrupting TMPRSS2-binding reduce TcsH toxicity in the intestinal epithelium of the female mice. These findings together shed light on the distinct molecular basis of TcsH-TMPRSS2 interactions, which expands our knowledge of host recognition mechanisms employed by LCTs and provides novel targets for developing therapeutics against P. sordellii infections. |
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手法 | EM (単粒子) |
解像度 | 3.0 - 6.0 Å |
構造データ | EMDB-36301, PDB-8jhz: ![]() EMDB-36302: The cryo-EM map of the C-terminal region in the TcsH-TMPRSS2 complex EMDB-36303, PDB-8ji0: |
化合物 | ![]() ChemComp-ZN: |
由来 |
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![]() | TOXIN/HYDROLASE / TcsH / TMPESS2 / TOXIN-HYDROLASE complex |