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Penn Scientists Show How Mistakes In Protein Folding Are Caught By "Protein Cages" Called Chaperonins

Date:
May 3, 1999
Source:
University Of Pennsylvania Medical Center
Summary:
It's imperative for all biological processes that proteins correctly maneuver from a simple string of amino acids to their pre-destined three-dimensional structure. This transformation -- called protein folding - is one of the most active areas of molecular biological research, and has taken on even more importance with the growing knowledge that misfolding can lead to such disorders as Alzheimer's disease, Huntington's disease, and prion-related neurodegenerative diseases.

It's imperative for all biological processes that proteins correctly maneuver from a simple string of amino acids to their pre-destined three-dimensional structure. This transformation -- called protein folding - is one of the most active areas of molecular biological research, and has taken on even more importance with the growing knowledge that misfolding can lead to such disorders as Alzheimer's disease, Huntington's disease, and prion-related neurodegenerative diseases. Recently, researchers at the University of Pennsylvania Medical Center have discovered how proteins called chaperonins protect cells from harm by sequestering and unfolding misshapened proteins. A report on this study appears in the April 30 issue of Science.

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"Proteins should know how to fold by themselves, but they sometimes get into trouble," says senior author S. Walter Englander, PhD, a professor of biochemistry and biophysics at the University of Pennsylvania School of Medicine. In times of stress, cells produce chaperonins, which are huge protein molecules that police other proteins that have misfolded as a result of any number of stressors -- including heat, heavy-metal poisoning, and ultraviolet radiation. If left unchecked, the misfolded proteins tend to clump, which can be harmful to normal cellular functions.

The Penn study looked specifically at a chaperonin called GroEL. "GroEL grabs the misfolded protein, engulfs it, pulls it open, and then throws it back out into the cytoplasm of the cell to fend for itself, " explains Englander. "The protein then takes its chances -- it may fold successfully, or it may get into trouble again." This entire process takes place within 13 seconds.

GroEL -- a sandwich of two circular proteins with a large central core into which average-sized proteins can fit - is able to capture thousands of different types of misfolded proteins. Its cavity is ringed with sites that bind nonspecifically to the hydrophobic, or water-avoiding, portions of proteins, which are normally found tucked deep inside a properly folded protein. "When a protein is misfolded and its hydrophobic insides are exposed, chaperonins snatch them up and help them to fold correctly by forcing them to unfold, so that they can try again," notes Englander.

In such protein misfolding disorders as mad cow's disease, chaperonins may fail to do their job correctly, but whether they come into play in the disease process is as yet unknown.

This work was conducted in the Johnson Research Foundation, a funding and research organization within Penn's Department of Biochemistry and Biophysics that concentrates on the study of physics as it applies to medicine.


Story Source:

The above story is based on materials provided by University Of Pennsylvania Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

University Of Pennsylvania Medical Center. "Penn Scientists Show How Mistakes In Protein Folding Are Caught By "Protein Cages" Called Chaperonins." ScienceDaily. ScienceDaily, 3 May 1999. <www.sciencedaily.com/releases/1999/05/990503041521.htm>.
University Of Pennsylvania Medical Center. (1999, May 3). Penn Scientists Show How Mistakes In Protein Folding Are Caught By "Protein Cages" Called Chaperonins. ScienceDaily. Retrieved November 27, 2014 from www.sciencedaily.com/releases/1999/05/990503041521.htm
University Of Pennsylvania Medical Center. "Penn Scientists Show How Mistakes In Protein Folding Are Caught By "Protein Cages" Called Chaperonins." ScienceDaily. www.sciencedaily.com/releases/1999/05/990503041521.htm (accessed November 27, 2014).

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