Dataset Information

Functional cooperativity between the trigger factor chaperone and the ClpXP proteolytic complex.

ABSTRACT: A functional association is uncovered between the ribosome-associated trigger factor (TF) chaperone and the ClpXP degradation complex. Bioinformatic analyses demonstrate conservation of the close proximity of tig, the gene coding for TF, and genes coding for ClpXP, suggesting a functional interaction. The effect of TF on ClpXP-dependent degradation varies based on the nature of substrate. While degradation of some substrates are slowed down or are unaffected by TF, surprisingly, TF increases the degradation rate of a third class of substrates. These include λ phage replication protein λO, master regulator of stationary phase RpoS, and SsrA-tagged proteins. Globally, TF acts to enhance the degradation of about 2% of newly synthesized proteins. TF is found to interact through multiple sites with ClpX in a highly dynamic fashion to promote protein degradation. This chaperone-protease cooperation constitutes a unique and likely ancestral aspect of cellular protein homeostasis in which TF acts as an adaptor for ClpXP.

SUBMITTER: Rizzolo K

PROVIDER: S-EPMC7804408 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Functional cooperativity between the trigger factor chaperone and the ClpXP proteolytic complex.

Rizzolo Kamran K Yu Angela Yeou Hsiung AYH Ologbenla Adedeji A Kim Sa Rang SR Zhu Haojie H Ishimori Koichiro K Thibault Guillaume G Leung Elisa E Zhang Yi Wen YW Teng Mona M Haniszewski Marta M Miah Noha N Phanse Sadhna S Minic Zoran Z Lee Sukyeong S Caballero Julio Diaz JD Babu Mohan M Tsai Francis T F FTF Saio Tomohide T Houry Walid A WA

Nature communications 20210112 1

A functional association is uncovered between the ribosome-associated trigger factor (TF) chaperone and the ClpXP degradation complex. Bioinformatic analyses demonstrate conservation of the close proximity of tig, the gene coding for TF, and genes coding for ClpXP, suggesting a functional interaction. The effect of TF on ClpXP-dependent degradation varies based on the nature of substrate. While degradation of some substrates are slowed down or are unaffected by TF, surprisingly, TF increases the ...[more]

PMID: 33436616

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Project description:ClpXP complex is an ATP-dependent mitochondrial matrix protease that binds, unfolds, translocates, and subsequently degrades specific protein substrates. Its mechanisms of operation are still being debated, and several have been proposed, including the sequential translocation of two residues (SC/2R), six residues (SC/6R), and even long-pass probabilistic models. Therefore, it has been suggested to employ biophysical-computational approaches that can determine the kinetics and thermodynamics of the translocation. In this sense, and based on the apparent inconsistency between structural and functional studies, we propose to apply biophysical approaches based on elastic network models (ENM) to study the intrinsic dynamics of the theoretically most probable hydrolysis mechanism. The proposed models ENM suggest that the ClpP region is decisive for the stabilization of the ClpXP complex, contributing to the flexibility of the residues adjacent to the pore, favoring the increase in pore size and, therefore, with the energy of interaction of its residues with a larger portion of the substrate. It is predicted that the complex may undergo a stable configurational change once assembled and that the deformability of the system once assembled is oriented, to increase the rigidity of the domains of each region (ClpP and ClpX) and to gain flexibility of the pore. Our predictions could suggest under the conditions of this study the mechanism of the interaction of the system, of which the substrate passes through the unfolding of the pore in parallel with a folding of the bottleneck. The variations in the distance calculated by molecular dynamics could allow the passage of a substrate with a size equivalent to ∼3 residues. The theoretical behavior of the pore and the stability and energy of binding to the substrate based on ENM models suggest that in this system, there are thermodynamic, structural, and configurational conditions that allow a possible translocation mechanism that is not strictly sequential.

Dataset Information

Functional cooperativity between the trigger factor chaperone and the ClpXP proteolytic complex.

Publications

Functional cooperativity between the trigger factor chaperone and the ClpXP proteolytic complex.

Similar Datasets

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