Structural basis of client specificity in mitochondrial membrane-protein chaperones
Posted 09 Jun 2020
bioRxiv DOI: 10.1101/2020.06.08.140772
Posted 09 Jun 2020
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 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 alltransmembrane 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 trans-membrane part are weaker than in TIM9·10. Consequently, TIM9·10 is outcompeting 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 vs . specificity. ### Competing Interest Statement The authors have declared no competing interest.
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