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PDBsum entry 4nkh
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References listed in PDB file
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Key reference
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Title
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Structure of an ssph1-Pkn1 complex reveals the basis for host substrate recognition and mechanism of activation for a bacterial e3 ubiquitin ligase.
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Authors
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A.F.Keszei,
X.Tang,
C.Mccormick,
E.Zeqiraj,
J.R.Rohde,
M.Tyers,
F.Sicheri.
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Ref.
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Mol Cell Biol, 2014,
34,
362-373.
[DOI no: ]
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PubMed id
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Abstract
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IpaH proteins are bacterium-specific E3 enzymes that function as type three
secretion system (T3SS) effectors in Salmonella, Shigella, and other
Gram-negative bacteria. IpaH enzymes recruit host substrates for ubiquitination
via a leucine-rich repeat (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 subdomain of
PKN1 in a manner that sterically displaces the catalytic domain from the LRR
domain, thereby activating catalytic function. SspH1 catalyzes the
ubiquitination and proteasome-dependent degradation of PKN1 in cells, which
attenuates androgen receptor responsiveness but not NF-κB 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 ubiquitin ligases.
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