--- res: bibo_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 vs. specificity.@eng bibo_authorlist: - foaf_Person: foaf_givenName: Iva foaf_name: Sučec, Iva foaf_surname: Sučec - foaf_Person: foaf_givenName: Yong foaf_name: Wang, Yong foaf_surname: Wang - foaf_Person: foaf_givenName: Ons foaf_name: Dakhlaoui, Ons foaf_surname: Dakhlaoui - foaf_Person: foaf_givenName: Katharina foaf_name: Weinhäupl, Katharina foaf_surname: Weinhäupl - foaf_Person: foaf_givenName: Tobias foaf_name: Jores, Tobias foaf_surname: Jores - foaf_Person: foaf_givenName: Doriane foaf_name: Costa, Doriane foaf_surname: Costa - foaf_Person: foaf_givenName: Audrey foaf_name: Hessel, Audrey foaf_surname: Hessel - foaf_Person: foaf_givenName: Martha foaf_name: Brennich, Martha foaf_surname: Brennich - foaf_Person: foaf_givenName: Doron foaf_name: Rapaport, Doron foaf_surname: Rapaport - foaf_Person: foaf_givenName: Kresten foaf_name: Lindorff-Larsen, Kresten foaf_surname: Lindorff-Larsen - foaf_Person: foaf_givenName: Beate foaf_name: Bersch, Beate foaf_surname: Bersch - foaf_Person: foaf_givenName: Paul foaf_name: Schanda, Paul foaf_surname: Schanda foaf_workInfoHomepage: http://www.librecat.org/personId=7B541462-FAF6-11E9-A490-E8DFE5697425 orcid: 0000-0002-9350-7606 bibo_doi: 10.1101/2020.06.08.140772 dct_date: 2020^xs_gYear dct_language: eng dct_publisher: Cold Spring Harbor Laboratory@ dct_title: Structural basis of client specificity in mitochondrial membrane-protein chaperones@ ...