![]() ![]() Most importantly, Hsp70s are involved in the regulation of the heat shock response in many proteobacteria ( Matsui et al., 2008 Kobayashi et al., 2011 Schumann, 2016 Schramm et al., 2017).įIGURE 1. For example, swimming, swarming, and twitching motility, cell adherence, expression of virulence factors and their injection into host cells, engulfment of the pathogen into phagocytosomes, and survival in endosomes were shown to depend on Hsp70s ( Köhler et al., 1996 Hanawa et al., 2002 Singh et al., 2007 Okuda et al., 2017 Collet et al., 2018). Hsp70s are also involved in virulence of many pathogenic bacteria. Hsp70s prevent formation of amyloids in the cytoplasm and assist secretion of the functional amyloid curli that is necessary for biofilm formation and cell adhesion ( Evans et al., 2011 Sugimoto et al., 2018). Hsp70s are important for the insertion of tail-anchored proteins into the plasma membrane ( Peschke et al., 2018). They disassemble native protein complexes like, for example, the λO-λP-DnaB complex during replication of bacteriophage λ ( Zylicz et al., 1989), the homodimeric replication initiation proteins RepA of P1 phages ( Wickner et al., 1991) and RepE of the mini-F plasmids ( Ishiai et al., 1994), and the dimeric RctB replication initiator of chromosome 2 in Vibrio cholerae ( Jha et al., 2017). To name just a few of their functions in bacteria, Hsp70s assist de-novo-folding of proteins interacting with nascent chains already at the ribosome ( Deuerling et al., 1999 Calloni et al., 2012), prevent aggregation of stress denatured proteins ( Mogk et al., 1999), and solubilize protein aggregates ( Goloubinoff et al., 1999) ( Figure 1A). The ATP-dependent 70 kDa heat shock proteins (Hsp70s) are without doubt the most versatile of all chaperones and involved in many diverse folding processes in the cell ( Meimaridou et al., 2009 Clerico et al., 2015). In this review I will discuss advances in the understanding of the molecular mechanism of the Hsp70 chaperone machinery focusing mostly on the bacterial Hsp70 DnaK and will compare the two other prokaryotic Hsp70s HscA and HscC with DnaK. Third, Hsp70s are targeted to their clients by a large number of cochaperones of the J-domain protein (JDP) family and the lifetime of the Hsp70-client complex is regulated by nucleotide exchange factors (NEF). Second, Hsp70 chaperones switch in a nucleotide-controlled manner between a state of low affinity for client proteins and a state of high affinity for clients. First, Hsp70s bind to short degenerate sequence motifs within their client proteins. Three mechanistic properties of Hsp70s are the basis for their high versatility. Through a multitude of functions Hsp70s are involved in many cellular control circuits for maintaining protein homeostasis and have been recognized as key factors for cell survival. None of the other main chaperone families (Tig, GroELS, HtpG, IbpA/B, ClpB) have been assigned with a comparable range of functions. The ATP-dependent Hsp70s are evolutionary conserved molecular chaperones that constitute central hubs of the cellular protein quality surveillance network. Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH-Alliance, Heidelberg, Germany. ![]()
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