Asset Details
Do you wish to reserve the book?
The structural basis of the activation and inhibition of DSR2 NADase by phage proteins
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
The structural basis of the activation and inhibition of DSR2 NADase by phage proteins
Do you wish to request the book?
The structural basis of the activation and inhibition of DSR2 NADase by phage proteins
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
The structural basis of the activation and inhibition of DSR2 NADase by phage proteins
2024
Overview
DSR2, a Sir2 domain-containing protein, protects bacteria from phage infection by hydrolyzing NAD
+
. The enzymatic activity of DSR2 is triggered by the SPR phage tail tube protein (TTP), while suppressed by the SPbeta phage-encoded DSAD1 protein, enabling phages to evade the host defense. However, the molecular mechanisms of activation and inhibition of DSR2 remain elusive. Here, we report the cryo-EM structures of apo DSR2, DSR2-TTP-NAD
+
and DSR2-DSAD1 complexes. DSR2 assembles into a head-to-head tetramer mediated by its Sir2 domain. The C-terminal helical regions of DSR2 constitute four partner-binding cavities with opened and closed conformation. Two TTP molecules bind to two of the four C-terminal cavities, inducing conformational change of Sir2 domain to activate DSR2. Furthermore, DSAD1 competes with the activator for binding to the C-terminal cavity of DSR2, effectively suppressing its enzymatic activity. Our results provide the mechanistic insights into the DSR2-mediated anti-phage defense system and DSAD1-dependent phage immune evasion.
This research shows how the bacterial protein DSR2, which protects against phage infection by degrading NAD
+
, is activated by phage protein TTP and inhibited by phage protein DSAD1 through cryo-EM studies and biochemical assays.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 64
/ 82/16
/ 82/80
/ 82/83
/ 96
/ Bacteria
/ Bacterial Proteins - chemistry
/ Bacterial Proteins - genetics
/ Bacterial Proteins - metabolism
/ Binding
/ Cavities
/ Holes
/ Humanities and Social Sciences
/ NAD
/ NAD+ Nucleosidase - chemistry
/ NAD+ Nucleosidase - metabolism
/ Phages
/ Proteins
/ Science
/ Viral Tail Proteins - chemistry
