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Proteins pack tighter in crowded native state
Date:11/12/2007

HOUSTON -- Nov. 12, 2007 -- The syrupy soup of proteins, ribosomes and membranes inside a living cell is so tightly packed it may increase the structural content of proteins by as much as 25 percent, according to new research from Rice University and the University of Houston (UH). The study is one of the first aimed at determining how the crowded environment inside a living cell affects protein structure.

"Based on accepted theories, we expected crowding to affect proteins in the unfolded state," said Rice biochemist Pernilla Wittung-Stafshede, one of the study's co-authors. "We were surprised when both experimental evidence and computer simulations showed that crowding also acts directly upon proteins in the folded state."

Living cells are crowded places. They're filled with a chemical soup of 100-300 mg per mL of large molecules, such as DNA, proteins and ribosomes. This corresponds to about 40 percent of volume occupancy.

"The consistency is very viscous," said Wittung-Stafshede. "It's something like Jell-O or the freeway at rush hour."

The study, which was co-authored by UH physicist Margaret Cheung, is available online and slated to appear in the Nov. 27 issue of the Proceedings of the National Academies of Science.

"Our simulations pinpointed specific places in the protein's structure where compaction was occurring and secondary structures improved," Cheung said. "This offers the first observed evidence -- both in silico and in vitro -- for structural effects on proteins in the native state."

To find out how crowded environments affect the stability, structure and folding of proteins, Wittung-Stafshede and Rice graduate student Loren Stagg set up a series of biophysical experiments involving the protein apoflavodoxin. This is an excellent model system because it is well-characterized in dilute conditions and can be made in the lab.

Using sucrose-based polymers (inert synthetic mimics of real macromolecules), the
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Contact: Jade Boyd
jadeboyd@rice.edu
713-348-6778
Rice University
Source:Eurekalert

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