Structural basis for DNA recognition by a viral genome-packaging machine

Maria Chechik, Sandra Joy Muriatu Greive, Alfred Aksel Antson*, Huw Thomas Jenkins*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

DNA recognition is critical for assembly of double-stranded DNA viruses, particularly for the initiation of packaging the viral genome into the capsid. The key component that recognises viral DNA is the small terminase protein. Despite prior studies, the molecular mechanism for DNA recognition remained elusive. Here we address this question by identifying the minimal site in the bacteriophage HK97 genome specifically recognised by the small terminase and determining the structure of this complex by cryoEM. The circular small terminase employs an entirely unexpected mechanism in which DNA transits through the central tunnel, and sequence-specific recognition takes place as it emerges. This recognition stems from a substructure formed by the N- and C-terminal segments of two adjacent protomers which are unstructured when DNA is absent. Such interaction ensures continuous engagement of the small terminase with DNA, enabling it to slide along the DNA while simultaneously monitoring its sequence. This mechanism allows locating and instigating packaging initiation and termination precisely at the specific cos sequence.
Original languageEnglish
Article numbere2406138121
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Volume121
Issue number33
DOIs
Publication statusPublished - 8 Aug 2024

Bibliographical note

© 2024 the Author(s)

Cite this