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Trans ‐targeting of protease substrates by conformationally activating a regulable ClpX‐recognition motif
Author(s) -
MarshallBatty Kimberly R.,
Nakai Hiroshi
Publication year - 2008
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2007.06099.x
Subject(s) - biology , repressor , signal transducing adaptor protein , mutant , alanine , protease , microbiology and biotechnology , biochemistry , biophysics , phosphorylation , amino acid , gene , enzyme , transcription factor
Summary Conversion of bacteriophage Mu repressor to ClpXP‐sensitive form correlates with induced local flexibility at the ClpX recognition motif located at the C‐terminal end. Changing the C‐terminal valine to an alanine (RepV196A) caused the degradation tag to be constitutively active like that of mutant repressors called Vir, which have a dominant ClpXP‐sensitive conformation. However, unlike Vir, RepV196A was unable to convert wild‐type repressor (Rep) to the ClpXP‐sensitive form. In mixtures with Rep, only RepV196A was rapidly degraded by ClpXP. Unlike Rep, RepV196A was ClpXP sensitive without induced C‐terminal flexibility. And unlike adaptor proteins that tether and deliver substrates to ClpX for trans ‐targeting, Vir promoted rapid degradation of Rep by ClpX deleted for the tethering site that binds adaptor proteins. Therefore, Rep's ClpX recognition motif has regulable properties, allowing an alternative trans ‐targeting mechanism in which an inactive degradation tag is turned on by induced conformational changes.