Hsp70 genes encode abundant heat-inducible 70-kDa hsps (hsp70s). In most eukaryotes hsp70 genes exist as part of
a multigene family. They are found in most cellular
compartments of eukaryotes including nuclei,
mitochondria, chloroplasts, the endoplasmic reticulum
and the cytosol, as well as in bacteria. The genes show a
high degree of conservation, having at least 5O% identity
(1). The N-terminal two thirds of hsp70s are more
conserved than the C-terminal third. Hsp70 binds ATP
with high affinity and possesses a weak ATPase activity
which can be stimulated by binding to unfolded proteins
and synthetic peptides (2). When hsc70 (constitutively
expressed) present in mammalian cells was truncated, ATP
binding activity was found to reside in an N-terminal fragment
of 44 kDa which lacked peptide binding capacity. Polypeptide
binding ability therefore resided within the C-terminal half
(3). The structure of this ATP binding domain displays multiple
features of nucleotide binding proteins (4).
All hsp70s, regardless of location, bind proteins, particularly
unfolded ones. The molecular chaperones of the hsp70 family
recognize and bind to nascent polypeptide chains as well as
partially folded intermediates of proteins preventing their
aggregation and misfolding. The binding of ATP triggers a
critical conformational change leading to the release of the
bound substrate protein (5). The universal ability of hsp70s to
undergo cycles of binding to and release from hydrophobic
stretches of partially unfolded proteins determines their role
in a great variety of vital intracellular functions such as
protein synthesis, protein folding and oligomerization and
protein transport.
PfHsp70-I (PF08_0054) is the major cytosolic Hsp70 in
Plasmodium falciparum. It is abundantly expressed in the
blood stages of the parasite and is thought to constitute 1-2%
of total parasite protein. It is induced upon heat shock. It is
present in the parasite in different complexes with PfHsp90
and some PfHsp40 (6, 7).