Nε-Fatty acylation of Rho GTPases by a MARTX toxin effector.
Yan ZhouChunfeng HuangLi YinMuyang WanXiaofei WangLin LiYanhua LiuZhao WangPanhan FuNi ZhangShe ChenXiaoyun LiuFeng ShaoYongqun ZhuPublished in: Science (New York, N.Y.) (2018)
The multifunctional autoprocessing repeats-in-toxin (MARTX) toxins are a family of large toxins that are extensively distributed in bacterial pathogens. MARTX toxins are autocatalytically cleaved to multiple effector domains, which are released into host cells to modulate the host signaling pathways. The Rho guanosine triphosphatase (GTPase) inactivation domain (RID), a conserved effector domain of MARTX toxins, is implicated in cell rounding by disrupting the host actin cytoskeleton. We found that the RID is an Nε-fatty acyltransferase that covalently modifies the lysine residues in the C-terminal polybasic region of Rho GTPases. The resulting fatty acylation inhibited Rho GTPases and disrupted Rho GTPase-mediated signaling in the host. Thus, RID can mediate the lysine Nε-fatty acylation of mammalian proteins and represents a family of toxins that harbor N-fatty acyltransferase activities in bacterial pathogens.
Keyphrases
- protein kinase
- smooth muscle
- escherichia coli
- regulatory t cells
- dendritic cells
- fatty acid
- induced apoptosis
- signaling pathway
- gram negative
- multidrug resistant
- single cell
- antimicrobial resistance
- drug delivery
- stem cells
- cell cycle arrest
- immune response
- cell therapy
- transcription factor
- amino acid
- bone marrow
- cell death
- pi k akt