CHAMPAIGN, lll. Blood clotting is a complicated business, particularly for those trying to understand how the body responds to injury. In a new study, researchers report that they are the first to describe in atomic detail a chemical interaction that is vital to blood clotting. This interaction between a clotting factor and a cell membrane has baffled scientists for decades.
The study appears online in the Journal of Biological Chemistry.
"For decades, people have known that blood-clotting proteins have to bind to a cell membrane in order for the clotting reaction to happen," said University of Illinois biochemistry professor James Morrissey, who led the study with chemistry professor Chad Rienstra and biochemistry, biophysics and pharmacology professor Emad Tajkhorshid. "If you take clotting factors off the membrane, they're thousands of times less active."
The researchers combined laboratory detective work with supercomputer simulations and solid-state nuclear magnetic resonance (SSNMR) to get at the problem from every angle. They also made use of tiny rafts of lipid membranes called nanodiscs, using an approach developed at Illinois by biochemistry professor Stephen Sligar.
Previous studies had shown that each clotting factor contains a region, called the GLA domain, which interacts with specific lipids in cell membranes to start the cascade of chemical reactions that drive blood clotting.
One study, published in 2003 in the journal Nature Structural Biology, indicated that the GLA domain binds to a special phospholipid, phosphatidylserine (PS), which is embedded in the membrane. Other studies had shown that PS binds weakly to the clotting factor o
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University of Illinois at Urbana-Champaign