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| Title | Cryo-EM and cryo-ET reveal the molecular architecture and host interactions of mycobacteriophage Douge. |
|---|---|
| Journal, issue, pages | Cell Rep, Vol. 44, Issue 8, Page 116057, Year 2025 |
| Publish date | Aug 26, 2025 |
Authors | Jitendra Maharana / Chun-Hsiung Wang / Li-An Tsai / Yi-Ting Liao / Cheng-Han Yang / Melvin C Shen / Lourriel S Macale / Thang Ngoc Tran / Joemark Narsico / Ronelito J Perez / Sunil Kumar Tewary / Jian-Li Wu / Hong-You Lin / Shu-Wei Chang / Aaron Franklin / Patrick J Moynihan / Deborah Jacobs-Sera / Krista G Freeman / Graham F Hatfull / Todd L Lowary / Meng-Chiao Ho / ![]() |
| PubMed Abstract | Recent reports highlight the efficacy of engineered mycobacteriophages to treat non-tuberculosis mycobacterial disease. Molecular insights into mycobacteriophage architecture and host interactions ...Recent reports highlight the efficacy of engineered mycobacteriophages to treat non-tuberculosis mycobacterial disease. Molecular insights into mycobacteriophage architecture and host interactions could allow structure-guided phage engineering to increase efficacy and broaden host range, but such information is currently unavailable. We describe the cryoelectron microscopy (cryo-EM) structure of mycobacteriophage Douge, which contains 1,105 protein subunits assembled into a complete siphophage and is coated with glycan-binding domains for mycobacterial cell surface interactions. When filled with viral genome, the channel spanning the connector, tail, and baseplate is sealed by tape measure proteins, providing a genome gating system and requiring limited structural changes for genome ejection upon phage-host contact. Nanometer-resolution cryoelectron tomography (cryo-ET) snapshots of phage-host interactions show that the baseplate remains attached to the mycobacterial outer membrane during viral genome ejection. This study reveals high-resolution structural details of this mycobacteriophage and its interaction with host glycans. |
External links | Cell Rep / PubMed:40711877 |
| Methods | EM (single particle) |
| Resolution | 2.18 - 6.03 Å |
| Structure data | EMDB-39973, PDB-8zdh: ![]() EMDB-39974: Focused refinement cryo-EM map of Mycobacteriophage Douge genome-packed capsid (Penton region: gp8) ![]() EMDB-39975: Focused refinement cryo-EM map of Mycobacteriophage Douge genome-packed capsid (P-hexon region: gp8 and gp113) ![]() EMDB-39976: Focused refinement cryo-EM map of Mycobacteriophage Douge genome-packed capsid (C-hexon region: gp8 and gp113) ![]() EMDB-39977: Composite cryo-EM map of Mycobacteriophage Douge genome-packed capsid (Penton, P-hexon and C-hexon region: gp8 and gp113) EMDB-39978, PDB-8zdi: ![]() EMDB-39979: Focused refinement cryo-EM map of Mycobacteriophage Douge genome-free capsid (Penton region: gp8) ![]() EMDB-39980: Focused refinement cryo-EM map of Mycobacteriophage Douge genome-free capsid (P-hexon region: gp8) ![]() EMDB-39981: Focused refinement cryo-EM map of Mycobacteriophage Douge genome-free capsid (C-hexon region: gp8) ![]() EMDB-39982: Composite cryo-EM map of Mycobacteriophage Douge genome-free capsid (Penton, P-hexon and C-hexon region: gp8) EMDB-39983, PDB-8zdj: EMDB-39984, PDB-8zdk: ![]() EMDB-39985: Focused refinement cryo-EM map of Mycobacteriophage Douge genome-packed connector (gp5 and gp9) ![]() EMDB-39986: Focused refinement cryo-EM map of Mycobacteriophage Douge genome-packed connector (gp10, gp12 and gp13) ![]() EMDB-39987: Focused refinement cryo-EM map of Mycobacteriophage Douge genome-packed connector (gp8 and gp113) ![]() EMDB-39988: Composite cryo-EM map of Mycobacteriophage Douge genome-packed connector-vertex (gp5, gp9, gp10, gp12, gp13, gp8 and gp113) EMDB-39989, PDB-8zdl: EMDB-39990, PDB-8zdm: ![]() EMDB-39991: Focused refinement cryo-EM map of Mycobacteriophage Douge genome-free connector (gp5 and gp9) ![]() EMDB-39992: Focused refinement cryo-EM map of Mycobacteriophage Douge genome-free connector (gp10, gp12 and gp13) ![]() EMDB-39993: Focused refinement cryo-EM map of Mycobacteriophage Douge genome-free connector (gp8) ![]() EMDB-39994: Composite cryo-EM map of Mycobacteriophage Douge genome-free connector-vertex (gp5, gp9, gp10, gp12, gp13 and gp8) EMDB-39995, PDB-8zdn: EMDB-39996, PDB-8zdo: ![]() EMDB-39997: Focused refinement cryo-EM map of Mycobacteriophage Douge baseplate (gp13) ![]() EMDB-39998: Focused refinement cryo-EM map of Mycobacteriophage Douge baseplate (gp17 and gp23) ![]() EMDB-39999: Focused refinement cryo-EM map of Mycobacteriophage Douge baseplate (gp16, gp18 and gp20) ![]() EMDB-60000: Composite cryo-EM map of Mycobacteriophage Douge baseplate (gp13, gp17, gp23, gp16, gp18 and gp20) EMDB-60001, PDB-8zdp: ![]() EMDB-60002: Focused refinement cryo-EM map of Mycobacteriophage Douge Central fiber (gp20, top region) ![]() EMDB-60003: Focused refinement cryo-EM map of Mycobacteriophage Douge central fiber (gp20, bottom region) ![]() EMDB-60004: Composite cryo-EM map of Mycobacteriophage Douge central fiber (gp20) EMDB-60005, PDB-8zdq: EMDB-60024, PDB-8zea: ![]() EMDB-60714: Cryo-EM structure of Mycobacteriophage Douge genome-packed connector-vertex (gp5, gp8, gp9, gp10, gp12, gp13 and gp113 ![]() EMDB-60715: Cryo-EM structure of Mycobacteriophage Douge genome-free connector vertex (gp5, gp8, gp9, gp10, gp12 and gp13) |
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Keywords | VIRUS / Mycobacteriophage / phage structure / Icosahedral / cryo-EM / protein assembly / VIRAL PROTEIN |
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