Deciphering the Roles of Multicomponent Recognition Signals by the AAA+ Unfoldase ClpX

Journal of Molecular Biology
Lorraine LingTania A Baker

Abstract

ATP-dependent protein remodeling and unfolding enzymes are key participants in protein metabolism in all cells. How these often-destructive enzymes specifically recognize target protein complexes is poorly understood. Here, we use the well-studied AAA+ unfoldase-substrate pair, Escherichia coli ClpX and MuA transposase, to address how these powerful enzymes recognize target protein complexes. We demonstrate that the final transposition product, which is a DNA-bound tetramer of MuA, is preferentially recognized over the monomeric apo-protein through its multivalent display of ClpX recognition tags. The important peptide tags include one at the C-terminus ("C-tag") that binds the ClpX pore and a second one (enhancement or "E-tag") that binds the ClpX N-terminal domain. We construct a chimeric protein to interrogate subunit-specific contributions of these tags. Efficient remodeling of MuA tetramers requires ClpX to contact a minimum of three tags (one C-tag and two or more E-tags), and that these tags are contributed by different subunits within the tetramer. The individual recognition peptides bind ClpX weakly (KD>70μM) but impart a high-affinity interaction (KD~1.0μM) when combined in the MuA tetramer. When the weak C-tag signal...Continue Reading

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Citations

Dec 19, 2015·Proceedings of the National Academy of Sciences of the United States of America·Bo-Eun Ahn, Tania A Baker
Sep 14, 2015·Journal of Molecular Biology·Marina Ostankovitch, Johannes Buchner
Oct 6, 2018·Molecular Microbiology·Jing LiuPeter Chien
Dec 8, 2015·Nature Reviews. Microbiology·Adrian O OlivaresRobert T Sauer

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