Chaperone Proteins Determine How Proteins Fold
Scientists identify DnaK as a key player in protein folding
Proteins are the molecular building blocks and machinery of cells involved in practically all biological processes. To fulfil their various functions, proteins need to be folded into complicated three-dimensional structures, each capable of then "locking" into position on DNA or RNA strands in order to complete their job.
Scientists from the Max Planck Institute of Biochemistry (MPIB) in Martinsried near Munich, Germany, have now analysed one of the key players of this folding process: the molecular chaperone DnaK.
“The understanding of these mechanisms is of great interest in the light of the many diseases in which folding goes awry, such as Alzheimer’s or Parkinson’s,” says Ulrich Hartl, MPIB director. The work of the researchers has now been published in Cell Reports.
Proteins are responsible for almost all biological functions. The cells of the human body continuously synthesise thousands of different proteins in the form of amino acid chains. In order to be biologically useful, these chains must fold into complex three-dimensional patterns. When this difficult process goes wrong, it can lead to useless or even dangerous protein clumps.
All cells, in bacteria or humans, have developed a network of molecular chaperones, proteins themselves, which help fold proteins properly.
MPIB scientists have now investigated the organisation of this network in the bacterium Escherichia coli. Using proteomic analyses they show how different chaperones cooperate during the folding process.
“We identified the Hsp70 protein DnaK as the central player of the network,” explains Ulrich Hartl. “It functions as a kind of turntable.”
DnaK binds to about 700 different protein chains as they are created. Furthermore, DnaK mediates the folding of most of these protein chains. Those it cannot fold are transferred to 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 to allow it to fold normally, protected from external influences.
The researchers also wanted to know what happens when the chaperone network is disturbed. For example, when GroEL is removed from a cell, its client proteins accumulate on DnaK. DnaK then shuttles those proteins to proteases where they are decomposed.
“Apparently, DnaK realises that the attached protein chains will never be able to mature into useful molecules,” says the biochemist.
Similar but even more complicated chaperone networks control the proteome [all proteins in a given type of cells; the term joins the words proteins and genome] of human cells. Understanding these reactions is of great interest as many neurodegenerative diseases result from folding gone awry.
Original article: http://www.mpg.de/5188655/key_player_protein_folding