Structural basis of client specificity in mitochondrial membrane-protein chaperones

I. Sučec, Y. Wang, O. Dakhlaoui, K. Weinhäupl, T. Jores, D. Costa, A. Hessel, M. Brennich, D. Rapaport, K. Lindorff-Larsen, B. Bersch, P. Schanda, BioRxiv (n.d.).


Preprint | Submitted | English
Author
Sučec, Iva; Wang, Yong; Dakhlaoui, Ons; Weinhäupl, Katharina; Jores, Tobias; Costa, Doriane; Hessel, Audrey; Brennich, Martha; Rapaport, Doron; Lindorff-Larsen, Kresten; Bersch, Beate; Schanda, PaulIST Austria
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Abstract
Chaperones are essential for assisting protein folding, and for transferring poorly soluble proteins to their functional locations within cells. Hydrophobic interactions drive promiscuous chaperone–client binding, but our understanding of how additional interactions enable client specificity is sparse. Here we decipher what determines binding of two chaperones (TIM8·13, TIM9·10) to different integral membrane proteins, the all-transmembrane mitochondrial carrier Ggc1, and Tim23 which has an additional disordered hydrophilic domain. Combining NMR, SAXS and molecular dynamics simulations, we determine the structures of Tim23/TIM8·13 and Tim23/TIM9·10 complexes. TIM8·13 uses transient salt bridges to interact with the hydrophilic part of its client, but its interactions to the transmembrane part are weaker than in TIM9·10. Consequently, TIM9·10 outcompetes TIM8·13 in binding hydrophobic clients, while TIM8·13 is tuned to few clients with both hydrophilic and hydrophobic parts. Our study exemplifies how chaperones fine-tune the balance of promiscuity <jats:italic>vs.</jats:italic> specificity.
Publishing Year
Date Published
2020-09-17
Journal Title
bioRxiv
IST-REx-ID

Cite this

Sučec I, Wang Y, Dakhlaoui O, et al. Structural basis of client specificity in mitochondrial membrane-protein chaperones. bioRxiv. doi:10.1101/2020.06.08.140772
Sučec, I., Wang, Y., Dakhlaoui, O., Weinhäupl, K., Jores, T., Costa, D., … Schanda, P. (n.d.). Structural basis of client specificity in mitochondrial membrane-protein chaperones. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.06.08.140772
Sučec, Iva, Yong Wang, Ons Dakhlaoui, Katharina Weinhäupl, Tobias Jores, Doriane Costa, Audrey Hessel, et al. “Structural Basis of Client Specificity in Mitochondrial Membrane-Protein Chaperones.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2020.06.08.140772.
I. Sučec et al., “Structural basis of client specificity in mitochondrial membrane-protein chaperones,” bioRxiv. Cold Spring Harbor Laboratory.
Sučec I, Wang Y, Dakhlaoui O, Weinhäupl K, Jores T, Costa D, Hessel A, Brennich M, Rapaport D, Lindorff-Larsen K, Bersch B, Schanda P. Structural basis of client specificity in mitochondrial membrane-protein chaperones. bioRxiv, 10.1101/2020.06.08.140772.
Sučec, Iva, et al. “Structural Basis of Client Specificity in Mitochondrial Membrane-Protein Chaperones.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2020.06.08.140772.
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