The dance of the chaperones: Scientists identify key player of protein folding

Mar 08, 2012

Proteins are the molecular building blocks and machinery of cells and involved in practically all biological processes. To fulfil their tasks, they need to be folded into a complicated three-dimensional structure. 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 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 . All cells, from bacteria to human, have therefore developed a network of molecular chaperones, proteins themselves, which help other proteins to fold properly.

MPIB scientists have now investigated the organisation of this network in the . 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 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 is temporarily enclosed and allowed to fold while protected from external influences.

Disruptions in the Chaperone Network

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 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 of human cells. Understanding these reactions is of great interest in the light of the many neurodegenerative diseases in which folding goes awry.

Explore further: Scientists create therapy-grade stem cells using new cocktail to reprogram adult cells

More information: G. Calloni, T. Chen, S.M. Schermann, H. Chang, P. Genevaux, F. Agostini, G.G. Tartaglia, M. Hayer-Hartl and F.U. Hartl: DnaK Functions as a Central Hub in the E. coli Chaperone Network. Cell Reports, March 8, 2012 DOI:10.1016/j.celrep.2011.12.007

Related Stories

Blame the 'chaperone'

Jan 07, 2011

A Jackson Laboratory research team led by Professor Patsy Nishina, Ph.D., has identified a mutation in a gene that's essential for correct protein-processing in cells. Defects in protein folding are associated with a variety ...

Unfolding 'nature's origami'

Mar 02, 2009

Sometimes known as "nature's origami", the way that proteins fold is vital to ensuring they function correctly. But researchers at the University of Leeds have discovered this is a 'hit and miss' process, with proteins potentially ...

'Snapshots' Shake Up Views about Proteins

Jun 14, 2006

In 2002, University of Maryland biochemist Victor Muñoz observed something about proteins that challenged the generally accepted theory about how proteins assume their biologically active states – a process called folding. ...

Shoe strings and egg openers

Nov 08, 2011

Photosynthesis is one of the most important biological processes. However, it is less efficient in plants than it could be. Red algae, in contrast, use a slightly different mechanism and are thus more productive. ...

Protein folding made easy

Jun 07, 2011

Protein folding has nothing to do with laundry. It is, in fact, one of the central questions in biochemistry. Protein folding is the continual and universal process whereby the long, coiled strings of amino ...

Recommended for you

Unraveling cell division

2 hours ago

CRG researchers shed new light on mitosis. The study published in the Journal of Cell Biology describes how Topo 2 disentangles DNA molecules and is essential for proper cell division

User comments : 0