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Mapping disordered proteins with single-molecule FRET
Published on July 31, 2019 53 min
A selection of talks on Biochemistry
The ERK1/2 MAPK cascade
- Prof. Melanie H. Cobb
- University of Texas Southwestern Medical Center at Dallas, USA
Amino acid conjugation: mechanism and enzymology
- Dr. Kathleen Knights
- Flinders University, Australia
My name is Hagen Hofmann and I have a research group here at the Weizmann Institute. In the following presentation, I will give a brief overview of how we can use single molecule fluorescence spectroscopy to study the properties of unfolded and intrinsically disordered proteins.
The study of unfolded proteins is the result of decades lasting investigation of one of the most fascinating processes in biomolecular sciences, the process of protein folding. Protein folding is the process in which a newly synthesized polypeptide chain forms a well-defined three-dimensional structure. Most cellular processes, but not all as you will see later in this talk, depends on the defined three-dimensional architecture of proteins. Folding itself is an enormously complex process that involves thousands of atoms. Even though some, mostly large proteins, require the help of chaperones to render folding effective, it has been shown in numerous experiments that indeed folding is autonomous. The importance of this process inspired researchers of a decades to identify the rules by which the three-dimensional structure of proteins is encoded in the amino acid sequence. In contrast to the genetic code though, the models in protein folding mainly come from chemistry and physics, and I will briefly review the two major strategies to describe protein folding.
The first strategy comes from chemistry, more precisely, from chemical kinetics. Here, the process of protein folding is seen as a series of coupled equilibria which means steps, in which the unfolded state U transforms while structurally defined intermediates I1 and I2 to the folded state, here denoted with F. In result, they exist in a well-defined paths to the folded state. The advantage of this U's that experimental folding candidates can be quantitatively described. An alternative and rather complimentary view of protein folding comes from statistical thermodynamics. Here, folding starts from a huge ensemble of unfolded conformers with high conformational entropy and high energy. During the folding process, the conformers lower their energy and entropy, which is often depicted as a float down a funnel whose axis are given by energy and entropy. In contrast to the defined passing chemical kinetics models, folding can take a multitude of parallel routes to the folded state at the bottom of the funnel. However, the two U's are not contradictory as you will show in a minute.