HOUSTON (Nov. 25, 2013) A method by Rice University researchers to model the way proteins fold and sometimes misfold has revealed branching behavior that may have implications for Alzheimer's and other aggregation diseases.
Results from the research will appear online this week in the Proceedings of the National Academy of Sciences.
In an earlier study of the muscle protein titin, Rice chemist Peter Wolynes and his colleagues analyzed the likelihood of misfolding in proteins, in which domains discrete sections of a protein with independent folding characteristics become entangled with like sequences on nearby chains. They found the resulting molecular complexes called "dimers" were often unable to perform their functions and could become part of amyloid fibers.
This time, Wolynes and his co-authors, Rice postdoctoral researcher Weihua Zheng and graduate student Nicholas Schafer, modeled constructs containing two, three or four identical titin domains. They discovered that rather than creating the linear connections others had studied in detail, these proteins aggregated by branching; the proteins created structures that cross-linked with neighboring proteins and formed gel-like networks that resemble those that imbue spider silk with its remarkable flexibility and strength.
"We're asking with this investigation, What happens after that first sticky contact forms?" Wolynes said. "What happens if we add more sticky molecules? Does it continue to build up further structure out of that first contact?
"It turned out this protein we've been investigating has two amyloidogenic segments that allow for branch structures. That was a surprise," he said.
The researchers used their AWSEM (Associative memory, Water-mediated Structure and Energy Model) program to analyze how computer models of muscle proteins interact with each other, particularly in various temperatures that determine when a protein is
|Contact: David Ruth|