Regulation of Nod1 by Hsp90 chaperone complex

Abstract

Nod1 and Nod2 proteins play important roles in mammalian innate immune responses as intracellular sensors for bacterial peptidoglycan. Nod1 and Nod2 share structural homology with many R proteins involved in plant disease resistance. It has been demonstrated that plant Hsp90 and its co-chaperone RAR1 are implicated in R-mediated disease resistance. Here the Chp-1 gene encoding a mammalian homologue of plant RAR1 was identified as a new target for transcriptional activation by heat shock factor 1 (HSF1), a stress-responsive HSF isoform. In addition, Nod1 is demonstrated to be a client protein of the Hsp90 chaperone complex containing the Chp-1. Chp-1 interacts with the tetratricopeptide repeat (TPR) domain of protein phosphatase 5 (PP5) and the ATPase domain of Hsp90 via two distinct zinc-binding cysteine and histidine rich domains (CHORDs). These findings suggest a common regulatory mechanism involving the Hsp90 chaperone complex in R-mediated disease resistance in plants and Nod1-mediated innate immune response in mammals.