Abstract
Molecular chaperones are central to cellular protein homeostasis. 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. 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. Yet, the balance between this promiscuity and some degree of client specificity is poorly understood. 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. We focus hereby on chaperone-client interactions that are independent of ATP. 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 discuss these features of chaperone-client complexes and possible factors that may contribute to this balance of promiscuity and specificity.
Highlights
Molecular chaperones are the essential components to ensure the protein homeostasis of the cell
How do chaperones achieve their ability to interact with many different client proteins efficiently while 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 fulllength client proteins have been characterized at the atomic level, and have thereby shed light onto the underlying interaction patterns
For the purposes of this review we focus on the holdase function of Trigger factor (TF) and in particular on one complex, the one with model client proteins, phosphotase A (PhoA), which was discussed as a client in SecB studies, and the aggregation-prone G32D/I33P variant of maltose-binding protein (MBP) Saio et al (2014)
Summary
Molecular chaperones are the essential components to ensure the protein homeostasis of the cell. 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). How do chaperones achieve their ability to interact with many different client proteins efficiently while retaining some kind of specificity? Dynamic Chaperone-Client Complexes quickly read only about the general common features that emerge from these examples to jump directly to section 6.
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