Structural Basis for the Differential Regulatory Roles of the PDZ Domain in C-Terminal Processing Proteases

MBio
Chuang-Kai ChuehChung-I Chang

Abstract

Carboxyl (C)-terminal processing proteases (CTPs) participate in protective and regulatory proteolysis in bacteria. The PDZ domain is central to the activity of CTPs but plays inherently different regulatory roles. For example, the PDZ domain inhibits the activity of the signaling protease CtpB by blocking the active site but is required for the activation of Prc (or Tsp), a tail-specific protease that degrades SsrA-tagged proteins. Here, by structural and functional analyses, we show that in the unliganded resting state of Prc, the PDZ domain is docked inside the bowl-shaped scaffold without contacting the active site, which is kept in a default misaligned conformation. In Prc, a hydrophobic substrate sensor distinct from CtpB engages substrate binding to the PDZ domain and triggers a structural remodeling to align the active-site residues. Therefore, this work reveals the structural basis for understanding the contrasting roles of the PDZ domain in the regulation of CTPs.IMPORTANCE Prc, also known previously as Tsp, is the founding member of the carboxyl-terminal processing protease (CTP) family of PDZ domain-containing proteases that include CtpA and CtpB. The substrate-binding PDZ domain is responsible for regulating the pr...Continue Reading

References

Dec 1, 1992·Journal of Bacteriology·A SeoaneS B Levy
Mar 1, 1993·Microbiological Reviews·A P Pugsley
Aug 31, 2000·Nature Structural Biology·D I LiaoB A Diner
Dec 26, 2001·Nucleic Acids Research·Neil D RawlingsAlan J Barrett
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Aug 25, 2006·Acta Crystallographica. Section D, Biological Crystallography·Kevin Cowtan
Feb 6, 2007·Journal of Bacteriology·Jack IwanczykJoaquin Ortega
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Brent O Cezairliyan, Robert T Sauer
Nov 6, 2007·Cell·Jungsan SohnRobert T Sauer
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Feb 18, 2011·Nature Reviews. Molecular Cell Biology·Tim ClausenMichael Ehrmann
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Garib N MurshudovAlexei A Vagin
Jul 25, 2012·Infection and Immunity·Chin-Ya WangChing-Hao Teng
May 31, 2014·PloS One·Eric SauvagePaulette Charlier
Aug 19, 2015·Proceedings of the National Academy of Sciences of the United States of America·Santosh Kumar SinghManjula Reddy
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor
Jan 1, 1997·Methods in Enzymology·Todd O Yeates
Jan 18, 2018·PLoS Biology·Samuel I Miller, Nina R Salama

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Methods Mentioned

BETA
thermal shift
PCR
column chromatography

Software Mentioned

UCSF Chimera system
PROCHECK
CCP4
GraphPad
Phaser
Phenix
HKL2000
GraphPad Prism
Sednterp
Xtriage

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