Molecular basis of Gabija anti-phage supramolecular assemblies

Xiao-Yuan Yang; Zhangfei Shen; Jiale Xie; Jacelyn Greenwald; Ila Marathe; Qingpeng Lin; Wen Jun Xie; Vicki H Wysocki; Tian-Min Fu

doi:10.1038/s41594-024-01283-w

Molecular basis of Gabija anti-phage supramolecular assemblies

Nat Struct Mol Biol. 2024 Apr 16. doi: 10.1038/s41594-024-01283-w. Online ahead of print.

Authors

Xiao-Yuan Yang^#^{1

2

3}, Zhangfei Shen^#^{1

2}, Jiale Xie^{1

2

3}, Jacelyn Greenwald⁴, Ila Marathe⁴, Qingpeng Lin^{1

2}, Wen Jun Xie⁵, Vicki H Wysocki⁴, Tian-Min Fu^{6

7

8}

Affiliations

¹ Department of Biological Chemistry and Pharmacology, Center for RNA Biology, The Ohio State University, Columbus, OH, USA.
² The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
³ Program of OSBP, The Ohio State University, Columbus, OH, USA.
⁴ Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, USA.
⁵ Department of Medicinal Chemistry, University of Florida, Gainesville, FL, USA.
⁶ Department of Biological Chemistry and Pharmacology, Center for RNA Biology, The Ohio State University, Columbus, OH, USA. Fu.978@osu.edu.
⁷ The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA. Fu.978@osu.edu.
⁸ Program of OSBP, The Ohio State University, Columbus, OH, USA. Fu.978@osu.edu.

^# Contributed equally.

PMID: 38627580
DOI: 10.1038/s41594-024-01283-w

Abstract

As one of the most prevalent anti-phage defense systems in prokaryotes, Gabija consists of a Gabija protein A (GajA) and a Gabija protein B (GajB). The assembly and function of the Gabija system remain unclear. Here we present cryo-EM structures of Bacillus cereus GajA and GajAB complex, revealing tetrameric and octameric assemblies, respectively. In the center of the complex, GajA assembles into a tetramer, which recruits two sets of GajB dimer at opposite sides of the complex, resulting in a 4:4 GajAB supramolecular complex for anti-phage defense. Further biochemical analysis showed that GajA alone is sufficient to cut double-stranded DNA and plasmid DNA, which can be inhibited by ATP. Unexpectedly, the GajAB displays enhanced activity for plasmid DNA, suggesting a role of substrate selection by GajB. Together, our study defines a framework for understanding anti-phage immune defense by the GajAB complex.