XThe ClpXP protease unfolds substrates using a constant rate of pulling but different gears

Maya Sen, Rodrigo A. Maillard, Kristofor Nyquist, Piere Rodriguez-Aliaga, Steve Pressé, Andreas Martin, Carlos Bustamante

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

ATP-dependent proteases are vital to maintain cellular protein homeostasis. Here, we study the mechanisms of force generation and intersubunit coordination in the ClpXP protease from E. coli to understand how these machines couple ATP hydrolysis to mechanical protein unfolding. Single-molecule analyses reveal that phosphate release is the force-generating step in the ATP-hydrolysis cycle and that ClpXP translocates substrate polypeptides in bursts resulting from highly coordinated conformational changes in two to four ATPase subunits. ClpXP must use its maximum successive firing capacity of four subunits to unfold stable substrates like GFP. The average dwell duration between individual bursts of translocation is constant, regardless of the number of translocating subunits, implying that ClpXP operates with constant "rpm" but uses different "gears."

Original languageEnglish (US)
Pages (from-to)636
Number of pages1
JournalCell
Volume155
Issue number3
DOIs
StatePublished - Oct 24 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Sen, M., Maillard, R. A., Nyquist, K., Rodriguez-Aliaga, P., Pressé, S., Martin, A., & Bustamante, C. (2013). XThe ClpXP protease unfolds substrates using a constant rate of pulling but different gears. Cell, 155(3), 636. https://doi.org/10.1016/j.cell.2013.09.022