Poster abstracts
Poster number 111 submitted by Zhangfei Shen
Assembly and activation mechanism of the SIR2-HerA anti-phage defense system
Zhangfei Shen (Department of Biological Chemistry and Pharmacology, The Center for RNA Biology, The Ohio State University, Columbus, OH), Xiao-Yuan Yang (Department of Biological Chemistry and Pharmacology, The Center for RNA Biology, The Ohio State University, Columbus, OH), Qingpeng Lin (Department of Biological Chemistry and Pharmacology, The Center for RNA Biology, The Ohio State University, Columbus, OH), Elizabeth Fosuah (Department of Biological Chemistry and Pharmacology, The Center for RNA Biology, The Ohio State University, Columbus, OH), Tian-Min Fu (Department of Biological Chemistry and Pharmacology, The Center for RNA Biology, The Ohio State University, Columbus, OH)
Abstract:
SIR2-HerA, a bacterial two-protein anti-phage defense system, induces bacterial death by depleting NAD+ upon phage infection. Biochemical reconstitution of SIR2, HerA, and the SIR2-HerA complex reveals a dynamic assembly process. Unlike other ATPases, HerA can form various oligomers, ranging from dimers to nonamers. When assembled with SIR2, HerA forms a hexamer and converts SIR2 from a nuclease to an NAD+ hydrolase, representing an unexpected regulatory mechanism mediated by protein assembly. Furthermore, high concentrations of ATP can inhibit NAD+ hydrolysis by the SIR2-HerA complex. Cryo-EM structures of the SIR2-HerA complex reveal a giant supramolecular assembly up to 1 MDa, with SIR2 as a dodecamer and HerA as a hexamer, crucial for anti-phage defense. Unexpectedly, the HerA hexamer resembles a spiral staircase and exhibits helicase activities toward dual-forked DNA. Together, we reveal the supramolecular assembly of SIR2-HerA as a unique mechanism for switching enzymatic activities and bolstering anti-phage defense strategies.
References:
Shen, Z., Lin, Q., Yang, X. Y., Fosuah, E., & Fu, T. M. (2023). Assembly-mediated activation of the SIR2-HerA supramolecular complex for anti-phage defense. Molecular Cell, 83(24), 4586-4599.
Keywords: HerA, SIR2, bacterial immunity