1. Structural Biology and Molecular Biophysics
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Protein Unfolding: Same structure, different mechanisms?

  1. Francis TF Tsai  Is a corresponding author
  2. Christopher P Hill  Is a corresponding author
  1. Department of Biochemistry and Molecular Biology, Baylor College of Medicine, United States
  2. Department of Biochemistry, University of Utah School of Medicine, United States
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Cite this article as: eLife 2020;9:e56501 doi: 10.7554/eLife.56501
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Figures

Structure of the ClpXP complex.

(A) Side and (B) top-down views of the ClpXP complex bound to a substrate (shown in orange). The six ClpX subunits are each shown in a different color (purple, blue, cyan, green, sage green, and yellow), with ATP shown in red and ADP in pink. The same colors are used throughout the figure. (C) Close-up side view of the pore region in ClpX with arrows indicating the proposed sequential (sage green arrow; Ripstein et al., 2020) and probabilistic (purple arrow; Fei et al., 2020) mechanisms. The tyrosines lining the ClpX pore are colored according to their corresponding ClpX subunit. Five of these tyrosines bind the substrate while the tyrosine of the yellow subunit, which is bound to ADP, does not contact the substrate. The ATP hydrolyzed in each of the models is indicated by a flash. In the sequential model (Ripstein et al., 2020), ATP hydrolysis in the lower subunit allows it to disengage from substrate, transition through the ‘yellow state’, exchange ADP for ATP, and bind the next two residues of the substrate by docking against the top-most subunit. Because each subunit binds two residues, the net result is ClpX ‘walking’ up the substrate and translocation of two substrate residues down toward ClpP. In the probabilistic model (Fei et al., 2020), ATP hydrolysis at the top position (sometimes preceded by hydrolysis at other positions) causes the upper subunit to maintain a tight grip on substrate and move it down toward the ‘yellow state’, thereby translocating substrate by approximately six residues toward ClpP.

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