4nkh
From Proteopedia
Crystal structure of SspH1 LRR domain
Structural highlights
FunctionSSPH1_SALT1 Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. This protein is an E3 ubiquitin ligase that interferes with host's ubiquitination pathway. Can ubiquitinate both ubiquitin and host PKN1. Down-modulates production of host proinflammatory cytokines by inhibiting NF-kappa-B-dependent gene expression, probably via interaction with PKN1.[1] [2] [3] [4] Publication Abstract from PubMedIpaH proteins are bacterial-specific E3 enzymes that function as T3SS effectors in Salmonella, Shigella, and other gram-negative bacteria. IpaH enzymes recruit host substrates for ubiquitination via an LRR domain, which can inhibit the catalytic domain in the absence of substrate. The basis for substrate recognition and the alleviation of autoinhibition upon substrate binding is unknown. Here we report the X-ray structure of Salmonella SspH1 in complex with human PKN1. The LRR domain of SspH1 interacts specifically with the HR1b coiled-coil sub-domain of PKN1 in manner that sterically displaces the catalytic domain from the LRR domain, and thereby activates catalytic function. SspH1 catalyzes the ubiquitination and proteasome-dependent degradation of PKN1 in cells, which attenuates androgen receptor responsiveness but not NF-kappaB activity. These regulatory features are conserved in other IpaH-substrate interactions. Our results explain the mechanism whereby substrate recognition and enzyme autoregulation are coupled in this class of bacterial effector proteins. Structure of an SspH1-PKN1 complex reveals the basis for host substrate recognition and mechanism of activation for a bacterial E3 ubiquitin ligase.,Keszei AF, Tang X, McCormick C, Zeqiraj E, Rohde JR, Tyers M, Sicheri F Mol Cell Biol. 2013 Nov 18. PMID:24248594[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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