Structural basis for effector transmembrane domain recognition by type VI secretion system chaperones
Type VI secretion systems (T6SSs) deliver antibacterial effector proteins between neighboring bacteria. Many effectors harbor N-terminal transmembrane domains (TMDs) implicated in effector translocation across target cell membranes. However, the distribution of these TMD-containing effectors remains...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/62816 |
| _version_ | 1811253152623624192 |
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| author | Shehryar Ahmad Kara K Tsang Kartik Sachar Dennis Quentin Tahmid M Tashin Nathan P Bullen Stefan Raunser Andrew G McArthur Gerd Prehna John C Whitney |
| author_facet | Shehryar Ahmad Kara K Tsang Kartik Sachar Dennis Quentin Tahmid M Tashin Nathan P Bullen Stefan Raunser Andrew G McArthur Gerd Prehna John C Whitney |
| author_sort | Shehryar Ahmad |
| collection | DOAJ |
| description | Type VI secretion systems (T6SSs) deliver antibacterial effector proteins between neighboring bacteria. Many effectors harbor N-terminal transmembrane domains (TMDs) implicated in effector translocation across target cell membranes. However, the distribution of these TMD-containing effectors remains unknown. Here, we discover prePAAR, a conserved motif found in over 6000 putative TMD-containing effectors encoded predominantly by 15 genera of Proteobacteria. Based on differing numbers of TMDs, effectors group into two distinct classes that both require a member of the Eag family of T6SS chaperones for export. Co-crystal structures of class I and class II effector TMD-chaperone complexes from Salmonella Typhimurium and Pseudomonas aeruginosa, respectively, reveals that Eag chaperones mimic transmembrane helical packing to stabilize effector TMDs. In addition to participating in the chaperone-TMD interface, we find that prePAAR residues mediate effector-VgrG spike interactions. Taken together, our findings reveal mechanisms of chaperone-mediated stabilization and secretion of two distinct families of T6SS membrane protein effectors. |
| first_indexed | 2024-04-12T16:46:21Z |
| format | Article |
| id | doaj.art-b93cc12a906b4c20b4bd3b8f3cbf9b48 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:46:21Z |
| publishDate | 2020-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-b93cc12a906b4c20b4bd3b8f3cbf9b482022-12-22T03:24:35ZengeLife Sciences Publications LtdeLife2050-084X2020-12-01910.7554/eLife.62816Structural basis for effector transmembrane domain recognition by type VI secretion system chaperonesShehryar Ahmad0https://orcid.org/0000-0002-2747-5212Kara K Tsang1https://orcid.org/0000-0001-7742-8855Kartik Sachar2https://orcid.org/0000-0003-4077-1734Dennis Quentin3https://orcid.org/0000-0003-3825-7066Tahmid M Tashin4Nathan P Bullen5Stefan Raunser6https://orcid.org/0000-0001-9373-3016Andrew G McArthur7Gerd Prehna8https://orcid.org/0000-0001-5539-7533John C Whitney9https://orcid.org/0000-0002-4517-8836Michael DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, CanadaMichael DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, CanadaDepartment of Microbiology, University of Manitoba, Winnipeg, CanadaDepartment of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, GermanyMichael DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, CanadaMichael DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, CanadaDepartment of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, GermanyMichael DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada; David Braley Centre for Antibiotic Discovery, McMaster University, Hamilton, CanadaDepartment of Microbiology, University of Manitoba, Winnipeg, CanadaMichael DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada; David Braley Centre for Antibiotic Discovery, McMaster University, Hamilton, CanadaType VI secretion systems (T6SSs) deliver antibacterial effector proteins between neighboring bacteria. Many effectors harbor N-terminal transmembrane domains (TMDs) implicated in effector translocation across target cell membranes. However, the distribution of these TMD-containing effectors remains unknown. Here, we discover prePAAR, a conserved motif found in over 6000 putative TMD-containing effectors encoded predominantly by 15 genera of Proteobacteria. Based on differing numbers of TMDs, effectors group into two distinct classes that both require a member of the Eag family of T6SS chaperones for export. Co-crystal structures of class I and class II effector TMD-chaperone complexes from Salmonella Typhimurium and Pseudomonas aeruginosa, respectively, reveals that Eag chaperones mimic transmembrane helical packing to stabilize effector TMDs. In addition to participating in the chaperone-TMD interface, we find that prePAAR residues mediate effector-VgrG spike interactions. Taken together, our findings reveal mechanisms of chaperone-mediated stabilization and secretion of two distinct families of T6SS membrane protein effectors.https://elifesciences.org/articles/62816molecular chaperonestype VI secretion systemx-ray crystallographyprotein transportGram-negative bacteriainterbacterial competition |
| spellingShingle | Shehryar Ahmad Kara K Tsang Kartik Sachar Dennis Quentin Tahmid M Tashin Nathan P Bullen Stefan Raunser Andrew G McArthur Gerd Prehna John C Whitney Structural basis for effector transmembrane domain recognition by type VI secretion system chaperones eLife molecular chaperones type VI secretion system x-ray crystallography protein transport Gram-negative bacteria interbacterial competition |
| title | Structural basis for effector transmembrane domain recognition by type VI secretion system chaperones |
| title_full | Structural basis for effector transmembrane domain recognition by type VI secretion system chaperones |
| title_fullStr | Structural basis for effector transmembrane domain recognition by type VI secretion system chaperones |
| title_full_unstemmed | Structural basis for effector transmembrane domain recognition by type VI secretion system chaperones |
| title_short | Structural basis for effector transmembrane domain recognition by type VI secretion system chaperones |
| title_sort | structural basis for effector transmembrane domain recognition by type vi secretion system chaperones |
| topic | molecular chaperones type VI secretion system x-ray crystallography protein transport Gram-negative bacteria interbacterial competition |
| url | https://elifesciences.org/articles/62816 |
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