Specification of Hsp70 Function by Type I and Type II Hsp40 - The Networking of Chaperones by Co-chaperones - page 91

Fig. 4.1 Model for regulation of the Hsp70 polypeptide binding and release cycle by Hsp40.
Hsp70 has low substrate affinity in the ATP bound state but upon hydrolysis of ATP stable Hsp-
70substrate complexes are formed. Hsp70-substrate complexes then disassociate upon regenera-
tion of Hsp70-ATP. In this model, Hsp40 acts to (1) deliver substrates to Hsp70 and (2) stimulate
the ATPase activity of Hsp70. This cycle is repeated numerous times until the substrate protein is
able to reach a native state. Co-chaperones such as the E3 ligase CHIP act downstream of Hsp40
to target Hsp70 clients to the proteasome for degradation
Kim et al. 2013 ; Cyr et al. 1994 ). These proteins were identified by the presence of a
conserved J-domain that stimulates the ATPase activity of the Hsp70 (Fig. 4.1 ; Cyr
et al. 1992 ; Liberek et al. 1991 ). Type I and Type II Hsp40s also have the conserved
ability to bind and deliver non-native proteins to Hsp70, which is essential for life
(Johnson and Craig 2001 ).
Type I Hsp40s are descendants of bacterial DnaJ and contain the J domain,
followed by a glycine/phenylalanine rich region (G/F), a zinc finger like region
(ZFLR), and a conserved C-terminal domain. The Type II Hsp40's are similar to
the type I Hsp40s, but instead of the zinc finger like region they contain a glycine/
methionine rich region. Type III Hsp40s contain the J-domain, but none of the other
conserved domains found in Type I or II Hsp40s. Instead, they often have special-
ized domains that localize them to certain areas of the cell and provide specificity
in substrate binding (Grove et al. 2011 ; Houck et al. 2014 ; Summers et al. 2013 ;
Douglas et al. 2009 ). Type I and Type II Hsp40s contain a C-terminal dimerization