We also refer to reviews on various aspects of chaperone-client complexes, e.g., those by Kim et al. We invite the reader who wants to quickly read only about the general common features that emerge from these examples to jump directly to section 6. In this review, we discuss the features of more than ten different chaperone systems, and provide insight into the interactions of these (predominantly folded) chaperones with their (predominantly unfolded) clients, and on how the balance of different types of interactions (hydrophobic, hydrophilic, electrostatic) may lay the basis for achieving some degree of promiscuity and some specificity. How do chaperones achieve their ability to interact with many different client proteins efficiently while also retaining some kind of specificity? And how do the interactions between chaperones and their clients enable the clients to be refolded, safely transported or even disaggregated from insoluble forms? During the last few years, several complexes of chaperones with their full-length client proteins have been characterized at the atomic level, and have thereby shed light onto the underlying interaction patterns. A central question in understanding chaperone function is how they interact with the polypeptides they bind, i.e., with their “client” proteins. There are many types and isoforms of chaperones in each cell, and they generally are organized in cooperating networks Balchin et al. Their importance is highlighted by their abundance in the cell: the family of 70 kDa heat-shock proteins (Hsp70) on its own, for example, is estimated to correspond to up to 3% of the total protein mass in eukaryotic cells under non-stress conditions Finka and Goloubinoff (2013). Molecular chaperones are the essential components to ensure the protein homeostasis of the cell. We discuss these features of chaperone-client complexes and possible factors that may contribute to this balance of promiscuity and specificity. The picture emerging from these studies highlights the importance of dynamics in these complexes, whereby several interaction types, not only hydrophobic ones, contribute to the complex formation. We focus hereby on chaperone-client interactions that are independent of ATP. Here, we review recent atomic-level descriptions of chaperones with client proteins, including chaperones in complex with intrinsically disordered proteins, with membrane-protein precursors, or partially folded client proteins. Yet, the balance between this promiscuity and some degree of client specificity is poorly understood. The dynamic nature also implies that a given chaperone can interact with many different client proteins, based on physico-chemical sequence properties rather than on structural complementarity of their (folded) 3D structure. Dynamic disorder is a key feature of the complexes of molecular chaperones and their client proteins, and it facilitates the client release towards a folded state or the handover to downstream components. Molecular chaperones are central to cellular protein homeostasis.
2Institute of Science and Technology Austria, Klosterneuburg, Austria.1CEA, CNRS, Institut de Biologie Structurale (IBS), Univ.Iva Sučec 1* Beate Bersch 1 Paul Schanda 1,2*
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