Proteins are responsible for almost all biological functions. The
cells of the human body continuously synthesize thousands of different proteins
in the form of amino acid chains. In order to be biologically useful, these
chains must fold into a complex three-dimensional pattern. When this difficult
process goes wrong, it can lead to useless or even dangerous protein clumps.
All cells, from bacteria to human, have therefore developed a network of
molecular chaperones, proteins themselves, which help other proteins to fold
properly.
Scientists have investigated the organisation of this network
in the bacterium Escherichia coli. Using proteomic analyses they show how
different chaperones cooperate during the folding process. They identified
the Hsp70 protein DnaK as the central player of the network, It functions as a kind of turntable. DnaK binds to
about 700 different protein chains as they are synthesised. Furthermore, DnaK
mediates the folding of most of these protein chains. Those it cannot fold are
transferred to yet another chaperone, the barrel-shaped GroEL. GroEL is a
highly specialised folding machine. It forms a nano-cage in which a single
protein chain is temporarily enclosed and allowed to fold while protected from
external influences.
The researchers also investigated what happens when the chaperone
network is disturbed. For example, when GroEL is removed from the cells, its
client proteins accumulate on DnaK, which then shuttles them to proteases to be
decomposed. "Apparently, DnaK realizes that the attached protein chains
will never be able to mature into useful molecules,".
Similar but even more complicated chaperone networks control the proteome of
human cells. Understanding these reactions is of great interest in the light of
the many neurodegenerative diseases in which folding goes awry.
