A Conserved Activation Cluster Is Required for Allosteric Communication in HtrA-Family Proteases
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Author(s)
de Regt, Anna K.
Kim, Seokhee
Sohn, Jungsan
Grant, Robert A.
Baker, Tania A.
Date Issued
February 2015
Journal
Structure
Publisher
Elsevier
Citation
de Regt, Anna K. et al. “A Conserved Activation Cluster Is Required for Allosteric Communication in HtrA-Family Proteases.” Structure 23.3 (2015): 517–526.
Version
Author's final manuscript
Abstract
In E. coli, outer-membrane stress causes a transcriptional response through a signaling cascade initiated by DegS cleavage of a transmembrane anti-sigma factor. Each subunit of DegS, an HtrAfamily protease, contains a protease domain and a PDZ domain. The trimeric protease domain is
autoinhibited by the unliganded PDZ domains. Allosteric activation requires binding of unassembled outer-membrane proteins (OMPs) to the PDZ domains and protein-substrate binding. Here, we identify a set of DegS residues that cluster together at subunit-subunit interfaces in the
trimer, link the active sites and substrate-binding sites, and are crucial for stabilizing the active enzyme conformation in response to OMP signaling. These residues are conserved across the HtrA-protease family, including orthologs linked to human disease, supporting a common
mechanism of allosteric activation. Indeed, mutation of residues at homologous positions in the DegP quality-control protease also eliminates allosteric activation.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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DOI of Published Version
https://doi.org/10.1016/j.str.2015.01.012
