Colleagues from Rice University, the University of Houston (UH) and University of Texas Health Science Center at Houston determine how a central binding protein calcium-calmodulin-dependent kinase II (CaMKII) binds and unbinds from the cytoskeleton of a neurons.
The team’s report the first clear details of how the binding sites of CaMKII act to align actin filaments the structural protein into long, rigid bundles. The bundles serve as the supporting skeletons of dendritic spines, spiky protrusions that receive chemical messages through synapses from other neurons.
Researchers aimed to understand how signals make their way through dendrites, the branches on nerve cells that transmit information between cells.
When they were done, the structure predicted by the computer was a remarkable match for two-dimensional electron microscope images by Waxham and his group that clearly show parallel actin filaments are held together, ladder-like, by rungs of CaMKII.
Actin molecules self-assemble into long, twisting filaments. The hydrophobic pockets between these molecules are perfectly configured to bind CaMKII, a large protein with multiple parts, or domains.
The team’s calculations showed the association domain is responsible for about 40% of the protein’s binding strength to actin.
A linker domain adds another 40% and the crucial regulatory domain provides the final 20% a sensible strategy, since the regulatory domain is on the lookout for incoming calcium-calmodulins that can unzip the entire protein from the filament.