Distinct static and dynamic interactions control ATPase-peptidase communication in a AAA+ protease

Mol Cell. 2007 Jul 6;27(1):41-52. doi: 10.1016/j.molcel.2007.05.024.

Abstract

In the ClpXP proteolytic machine, ClpX uses the energy of ATP hydrolysis to unfold protein substrates and translocate them through a central pore and into the degradation chamber of ClpP. Here, we demonstrate a bipartite system of ClpX-ClpP interactions that serves multiple functional roles. High-affinity contacts between six loops near the periphery of the hexameric ClpX ring and a ClpP ring establish correct positioning and increase degradation activity but are insensitive to nucleotide state. These static peripheral interactions maintain a stable ClpXP complex, while other parts of this machine change conformation hundreds of times per minute. By contrast, relatively weak axial contacts between loops at the bottom of the ClpX central channel and N-terminal loops of ClpP vary dynamically with the nucleotide state of individual ClpX subunits, control ATP-hydrolysis rates, and facilitate efficient protein unfolding. Thus, discrete static and dynamic interactions mediate binding and communication between ClpX and ClpP.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Adenosine Triphosphatases / chemistry
  • Adenosine Triphosphatases / metabolism*
  • Adenosine Triphosphate / metabolism
  • Amino Acid Sequence
  • Endopeptidase Clp / chemistry
  • Endopeptidase Clp / metabolism*
  • Escherichia coli / enzymology*
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / metabolism*
  • Hydrolysis
  • Models, Molecular
  • Molecular Chaperones / chemistry
  • Molecular Chaperones / metabolism*
  • Molecular Sequence Data
  • Mutation / genetics
  • Protein Binding
  • Protein Folding
  • Protein Processing, Post-Translational
  • Protein Structure, Secondary
  • RNA, Bacterial / metabolism
  • Substrate Specificity
  • Terminology as Topic

Substances

  • Escherichia coli Proteins
  • Molecular Chaperones
  • RNA, Bacterial
  • tmRNA
  • Adenosine Triphosphate
  • ClpP protease, E coli
  • Endopeptidase Clp
  • Adenosine Triphosphatases
  • ClpX protein, E coli
  • ATPases Associated with Diverse Cellular Activities