mohammad tabish ahmed - eTheses Repository - University of ...

Chapter 1
Group 1: ClpA (Hsp104), ClpB, ClpC, ClpD, ClpE have two nucleotide binding
domains
Group 2: ClpX and ClpY have one nucleotide binding domain.
Both these groups can then be further subdivided based on specific signature motifs or by the
length of the interdomain regions separating the two nucleotide binding domains (Schirmer et
al., 1996).
Structurally, all Hsp100 chaperones contain a conserved core, referred to as the AAA
module, which consists of two nucleotide binding subdomains (NBD) (Maurizi & Xia, 2004).
This area is the binding site for ATP and also contains the catalytic residues for hydrolysis
(Lupas & Martin, 2002). The N-domain of the Hsp100 chaperones is not essential for all its
members. Hsp78, which is a homologue of ClpB, does not have an N-domain but is active as
a chaperone (Krzewska et al., 2001). However, it is at this domain that the adapter protein
ClpS associates on ClpA to alter its substrate specificity (Dougan et al., 2002). It is the I-
domain that is responsible for the biological activity of the Hsp100 chaperones. Deleting this
region causes the proteins to lose the ability to hydrolyse ATP (Mogk et al., 2003). A general
representation of the mechanism by which some of the Hsp100 chaperones function is shown
in figure 1.13.
33