TY - JOUR

T1 - The N-Terminal Domain of Tailspike Depolymerases Affects the Replication Efficiency of Synthetic Klebsiella Phages

AU - Baykov, Ivan K.

AU - Mikhaylova, Ekaterina E.

AU - Miroshnikova, Anna V.

AU - Fedorets, Valeriya A.

AU - Markova, Sofya A.

AU - Ushakova, Tatyana A.

AU - Morozova, Vera V.

AU - Tikunova, Nina V.

N1 - This research was funded by the Russian Science Foundation, grant number 24-24-00553.

PY - 2025/11/22

Y1 - 2025/11/22

N2 - Bacteriophage receptor-binding proteins are often attached to the tail via a conserved N-terminal adapter/anchor domain, presumed to function independently from the distal receptor-binding/catalytic domain. Using synthetic phage technology, we demonstrated that the N-terminal domain in Przondovirus phages KP192 and KP195 substantially modulates the receptor-binding and hydrolytic activities of their type A tailspikes. A bioinformatics analysis of related proteins revealed a high correlation between the N-terminal domain and the distal receptor-binding region. Furthermore, it was shown that an imperfect structural fit between the N-terminal domain and the adjacent tail proteins (gatekeeper and nozzle proteins) can reduce virion assembly efficiency, thereby impairing phage fitness. These results underscore the importance of selecting an appropriate N-terminal domain of receptor-binding proteins when engineering bacteriophages with altered host specificity.

AB - Bacteriophage receptor-binding proteins are often attached to the tail via a conserved N-terminal adapter/anchor domain, presumed to function independently from the distal receptor-binding/catalytic domain. Using synthetic phage technology, we demonstrated that the N-terminal domain in Przondovirus phages KP192 and KP195 substantially modulates the receptor-binding and hydrolytic activities of their type A tailspikes. A bioinformatics analysis of related proteins revealed a high correlation between the N-terminal domain and the distal receptor-binding region. Furthermore, it was shown that an imperfect structural fit between the N-terminal domain and the adjacent tail proteins (gatekeeper and nozzle proteins) can reduce virion assembly efficiency, thereby impairing phage fitness. These results underscore the importance of selecting an appropriate N-terminal domain of receptor-binding proteins when engineering bacteriophages with altered host specificity.

UR - https://www.scopus.com/pages/publications/105024641236

UR - https://www.mendeley.com/catalogue/062bfc55-44ba-3375-ad26-d795e19ba1f7/

U2 - 10.3390/ijms262311297

DO - 10.3390/ijms262311297

M3 - Article

C2 - 41373458

VL - 26

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 23

M1 - 11297

ER -