期刊
NATURE STRUCTURAL & MOLECULAR BIOLOGY
卷 11, 期 9, 页码 868-876出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb818
关键词
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资金
- NIAID NIH HHS [AI-30162, R21 AI146481] Funding Source: Medline
ExoS and ExoT are bifunctional type III cytotoxins of Pseudomonas aeruginosa that contain an N-terminal RhoGAP domain and a C-terminal ADP-ribosylation domain. Although they share 76% amino acid identity, ExoS and ExoT ADP-ribosylate different substrates. Using protein modeling and site-directed mutagenesis, the regions of ExoS and ExoT that define substrate specificity were determined. Regions B ( active site loop), C (ARTT motif) and E (PN loop) on ExoS are necessary and sufficient to recognize ExoS targets, whereas regions B, C and E on ExoT are necessary but not sufficient to recognize ExoT targets, such as the Crk proteins. A specific Crk recognition motif on ExoT was defined as region A ( helix alpha1). The electrostatic properties of regions A, B, C and E define the substrate specificity of ExoS and ExoT and these interactions can explain how other bacterial ADP-ribosylating toxins recognize their unique substrates.
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