Discovery of 7 times higher complexity of protein folding!
|March 5, 2017||Posted by DLH under Biophysics, Cell biology, Design inference, Informatics, Intelligent Design, Proteome|
Can protein folding complexity be formed by stochastic processes? With 14 intermediate steps?
JILA Team Discovers Many New Twists in Protein Folding
Biophysicists at JILA have measured protein folding in more detail than ever before, revealing behavior that is surprisingly more complex than previously known. . . .
They fold into three-dimensional shapes that determine their function through a series of intermediate states, like origami. Accurately describing the folding process requires identifying all of the intermediate states.
The JILA research revealed many previously unknown states by unfolding an individual protein. For example, the JILA team identified 14 intermediate states—seven times as many as previously observed—in just one part of bacteriorhodopsin, a protein in microbes that converts light to chemical energy and is widely studied in research.
“The increased complexity was stunning,” said project leader Tom Perkins, a National Institute of Standards and Technology (NIST) biophysicist working at JILA, a partnership of NIST and the University of Colorado Boulder. “Better instruments revealed all sorts of hidden dynamics that were obscured over the last 17 years when using conventional technology.”
“If you miss most of the intermediate states, then you don’t really understand the system,” he said.
Knowledge of protein folding is important because proteins must assume the correct 3-D structure to function properly. Misfolding may inactivate a protein or make it toxic. Several neurodegenerative and other diseases are attributed to incorrect folding of certain proteins.
Hidden dynamics in the unfolding of individual bacteriorhodopsin proteins. 2017. H. Yu, M.G.W. Siewny, D.T. Edwards, A.W. Sanders and T.T. Perkins. Science. March 3. Vol. 355, Issue 6328, pp. 945-950, DOI: 10.1126/science.aah7124
Pulling apart protein unfolding
Elucidating the details of how complex proteins fold is a longstanding challenge. Key insights into the unfolding pathways of diverse proteins have come from single-molecule force spectroscopy (SMFS) experiments in which proteins are literally pulled apart. Yu et al. developed a SMFS technique that could unfold individual bacteriorhodopsin molecules in a native lipid bilayer with 1-µs temporal resolution (see the Perspective by Müller and Gaub). The technique delivered a 100-fold improvement over earlier studies of bacteriorhodopsin and revealed many intermediates not seen before. The authors also observed unfolding and refolding transitions between intermediate states.