A new topology of the HK97-like fold revealed in Bordetella bacteriophage by cryoEM at 3.5 Å resolution
Xing Zhang,
Huatao Guo,
Lei Jin,
Elizabeth Czornyj,
Asher Hodes,
Wong H Hui,
Angela W Nieh,
Jeff F Miller,
Z Hong Zhou
Affiliations
Xing Zhang
California NanoSystems Institute, University of California, Los Angeles, Los Angeles, United States
Huatao Guo
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States
Lei Jin
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States
Elizabeth Czornyj
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States
Asher Hodes
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States
Wong H Hui
California NanoSystems Institute, University of California, Los Angeles, Los Angeles, United States
Angela W Nieh
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States
Jeff F Miller
California NanoSystems Institute, University of California, Los Angeles, Los Angeles, United States; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States
Z Hong Zhou
California NanoSystems Institute, University of California, Los Angeles, Los Angeles, United States; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States
Bacteriophage BPP-1 infects and kills Bordetella species that cause whooping cough. Its diversity-generating retroelement (DGR) provides a naturally occurring phage-display system, but engineering efforts are hampered without atomic structures. Here, we report a cryo electron microscopy structure of the BPP-1 head at 3.5 Å resolution. Our atomic model shows two of the three protein folds representing major viral lineages: jellyroll for its cement protein (CP) and HK97-like (‘Johnson’) for its major capsid protein (MCP). Strikingly, the fold topology of MCP is permuted non-circularly from the Johnson fold topology previously seen in viral and cellular proteins. We illustrate that the new topology is likely the only feasible alternative of the old topology. β-sheet augmentation and electrostatic interactions contribute to the formation of non-covalent chainmail in BPP-1, unlike covalent inter-protein linkages of the HK97 chainmail. Despite these complex interactions, the termini of both CP and MCP are ideally positioned for DGR-based phage-display engineering.
