Identification of a distinct substrate-binding domain in the bacterial cysteine methyltransferase effectors NleE and OspZ

Abstract

The type III secretion system effector protein NleE from enteropathogenic Escherichia coli plays a key role in the inhibition of NF-ΚB activation during infection. NleE inactivates the ubiquitin chain binding activity of host proteins TAK1-binding proteins 2 and 3 (TAB2 and TAB3) by modifying the Npl4 zinc finger domain through S-adenosyl methionine-dependent cysteine methylation. Using yeast two-hybrid protein interaction studies, we found that a conserved region between amino acids 34 and 52 of NleE, in particular the motif49 GITR52 , was critical for TAB2 and TAB3 binding. NleE mutants lacking49 GITR52 were unable to methylate TAB3, and wild type NleE but not NleE49AAAA52 where each of GI..