Life's unbearable complexity – Biologisk Institut - Københavns Universitet

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21. februar 2018

Life's unbearable complexity

Protein Research

In the molecular world, the building blocks of life have always been appreciated as intricate and complex. Nonetheless, structural biology have until now worked with a degree of order amidst the chaos, as protein function was defined by structure and order. This is no longer the case.

Order and structure have always served as a basis for understanding the interactions and communications among proteins, genes and cells. Proteins are ordered into highly specific structures and their molecules come in pairs, where one acts as a lock, and the other as a molecular key. A research team composed of researchers from the University of Copenhagen, the University of Zurich, and the National Institutes of Health in the US have discovered a surprising phenomenon in molecular communication and their results have just been published in Nature.

“Together with our international collegues, we have demonstrated that two proteins, without the formation or involvement of an ordered surface, can form an extremely strong complex that is maintained in a fully dynamic state. The decisive factor is the highly opposing charges of the proteins. Communications between the two proteins is important for the reading of our DNA”, according to Professor Birthe B. Kragelund of the University of Copenhagen’s Department of Biology.

The research also highlights that there are many other proteins in the human proteome that might form similar complexes. This new protein interaction mechanism opens the door to a wide range of possibilities for protein composition and function that was previously considered impossible. While the phenomenon that gives rise to these so-called polyelectrolyte complexes is known from physics and polymer chemistry, their structural and dynamic properties remain unclear.

Over the past 10-20 years, the discovery of functional proteins lacking fixed or three-dimensional order, known as intrinsically disordered proteins - IDPs, has challenged the understanding of molecular communication. For instance, observations of antibodies that recognized and then bound themselves to unstructured regions had been made, and disorder within complexes described, but researchers always assumed that at least one of the molecules in a given discrete complex had a well-defined structure.

“Nuclear magnetic resonance spectroscopy, an area of expertise in the SBiNLab research group at the University of Copenhagen’s Department of Biology, is particularly well-suited for studying the structural properties of disordered proteins. But it is the unique combination of this technique along with single-molecule fluorescence spectroscopy and computer simulation that has precipitated the description of this first fully dynamic protein complex,” according to Postdoc Katrine Bugge of SBiNLab, one of the lead authors.

The decoding of thiese new molecular principles begun by the research team presents wide-ranging opportunities for the design of future molecules with respect to everyday consumer products like dairy products, and above all, towards the development of improved pharmaceuticals and medicines.