Abstract
AbstractLegionella pneumophilais a facultative intracellular pathogen that causes Legionnaires’ disease or Pontiac fever in humans upon accidental inhalation ofLegionella-contaminated aerosols. During infection,L. pneumophilasecretes more than 300 effectors into the host for the biogenesis of a replication-permissive niche, known as theLegionella containingvacuole (LCV). Among these, a large number of effectors harbor protein domains that recognize specific phosphoinositide (PI) lipids and mediate the anchoring of these effectors to the surface of LCV or other host membrane-bound organelles. TheLegionellaeffector SetA contains a unique C-terminal domain (SetA-CTD) that has been shown to specifically bind with phosphatidylinositol-3-phosphate (PI(3)P) and target SetA to endosomes and LCVs. Here, we report the NMR solution structure of SetA-CTD, which mainly comprises a four α-helix bundle. The structure reveals a basic pocket at one end of the α-helix bundle for PI(3)P binding and two hydrophobic loops for membrane insertion. Mutations of key residues involved in lipid binding result in the loss of SetA in membrane association and endosomal localization. Structural comparison with other PI(3)P-binding domains highlights a general theme applied by multiple families of phosphoinositide-binding domains across species.
Publisher
Cold Spring Harbor Laboratory
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献