{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:39:14Z","timestamp":1785404354443,"version":"3.56.0"},"posted":{"date-parts":[[2025,6,12]]},"group-title":"Biochemistry","reference-count":90,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T00:00:00Z","timestamp":1749686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["GM100888"],"award-info":[{"award-number":["GM100888"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["GM140733"],"award-info":[{"award-number":["GM140733"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,6,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Cryogenic electron microscopy (cryo-EM) analysis of bacteriophages is a valuable method for deciphering virus composition and conformational plasticity. In this study, we present a high-resolution structural atlas of the\n                  <jats:italic>Pseudomonas<\/jats:italic>\n                  virus Pa223, a phage from the\n                  <jats:italic>Bruynoghevirus<\/jats:italic>\n                  genus that has recently been used in clinical cocktails for treating cystic fibrosis and non-cystic fibrosis bronchiectasis, as well as for compassionate care. By combining bioinformatics, proteomics, cryo-EM single particle analysis, and localized reconstruction, we annotated and built atomic models for eight structural polypeptide chains that form the icosahedral capsid and noncontractile tail. We discovered that the Pa223 capsid is decorated by a spike protein that features a unique triple-\u03b2 helix fold with no structural homologs in the database. The Pa223 tail features six trimeric tail fibers extending upwards, similar to, but shorter than, those found in phage T7. Unlike T7, the Pa223 tail is extended by two head-to-tail adaptors and sealed by a trimeric tail needle, similar to P22-like phages. We identified a protein bound around the outer perimeter of the portal protein, positioned similarly to the ejection protein gp72, which was identified in the\n                  <jats:italic>Pseudomonas<\/jats:italic>\n                  phage DEV, a\n                  <jats:italic>Litunavirus<\/jats:italic>\n                  phage and member of the reclassified\n                  <jats:italic>Schitoviridae<\/jats:italic>\n                  family. This structural hint led us to identify the Pa223 ejection proteins gp53, gp54, and gp56, which bioinformatically resemble those of T7-like phages more closely than\n                  <jats:italic>Schitoviridae<\/jats:italic>\n                  . Thus, phage Pa223 contains diverse structural elements found in P22-like, T7-like, and\n                  <jats:italic>Litunavirus<\/jats:italic>\n                  phages, providing a framework for understanding the diversification and evolution of ejection proteins in\n                  <jats:italic>Bruynogheviruses<\/jats:italic>\n                  .\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>\n                        The high-resolution structure of\n                        <jats:italic>Bruynoghevirus<\/jats:italic>\n                        Pa223 reveals hybrid structural features that are shared among P22-like, T7-like, and\n                        <jats:italic>Litunavirus<\/jats:italic>\n                        phages.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>The Pa223 capsid is decorated with a trimeric spike asymmetrically bound at the icosahedral 3-fold axes.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>The Pa223 tail features two quasi-equivalent conformations of the head-to-tail adaptor protein arranged into two coaxial rings.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        Identification of the ejection protein gp54 through structural similarity to gp72 from the\n                        <jats:italic>Litunavirus<\/jats:italic>\n                        DEV.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Bioinformatic mapping of the Pa223 ejection proteins gp53 and gp56 validated through mass spectrometry analysis of infectious virions.<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.1101\/2025.06.11.659172","type":"posted-content","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T00:35:11Z","timestamp":1749774911000},"source":"Crossref","is-referenced-by-count":0,"title":["High-resolution cryo-EM analysis of the therapeutic\n                  <i>Pseudomonas<\/i>\n                  phage Pa223"],"prefix":"10.64898","author":[{"given":"Chun-Feng David","family":"Hou","sequence":"first","affiliation":[{"name":"Department of Chemistry and Chemical Biology, Rutgers, the State University of New Jersey, Piscataway, NJ, 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Bellis","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, 1825 University Blvd, Birmingham, AL 35294, 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