G proteins play a central role in cellular signal processing. They are described as molecular switches that oscillate between ‘on’ and ‘off’, regulated by effectors. Biochemists at Heidelberg University have now gained fundamental insights into the mechanics of these switches. By studying the flagella, the organelles of locomotion in bacteria, researchers were able to identify an effector that turns a specific G protein ‘off’. They succeeded in visualising this process through X-ray crystallography. Their research results also provide insight into the evolution from the world of RNA to the “modern” world of proteins.
Bacteria need to be mobile to react to environmental changes, and in the case of pathogens, to reach the site of infection. Flagella are the organelles of locomotion in bacteria and the tiniest motors in the biosphere. When cells divide, the exact position of the new flagellum needs to be determined each time. The G protein FlhF is responsible for that task. FlhF is a molecular switch that apparently needed no effectors. “In our study, however, we identified a protein that assumes the effector role and were able to describe its mode of action, thereby fundamentally altering this previously held view”, explains Prof. Dr. Irmgard Sinning of the Heidelberg University Biochemistry Center. The G protein FlhF, together with a signal sequence binding protein (SRP54) and its receptor (FtsY), constitutes the ancient family of SRP-GTPases, which consists solely of these three proteins and is responsible for the transport of proteins in or through a biological membrane. In all known organisms, SRP54 and FtsY regulate the transport of proteins using the signal recognition particle (SRP). Although the SRP system is already well understood, it was recently demonstrated that the protein SRP54 and the receptor FtsY interact with the SRP RNA in a way reminiscent of FlhF and its newly discovered effector. “Our study of the G protein FlhF not only offers an explanation for the FlhF effector complex, it also integrates this knowledge into a general concept of SRP-GTPase activation through RNA or proteins”, says Dr. Gert Bange of the Heidelberg University Biochemistry Center. “We used FlhF to demonstrate how the ‘modern’ protein world replaced the original RNA world by means of a strikingly simple modification.” The results of the research were published in “Nature Structural & Molecular Biology”.
Original publication:G. Bange, N. Kümmerer, P. Grudnik, R. Lindner, G. Petzold, D. Kressler, E. Hurt, K. Wild, I. Sinning: Structural basis for the molecular evolution of SRP-GTPase activation by protein. Nat Struct Mol Biol. 2011, 18(12):1376-80. doi: 10.1038/nsmb.2141More informationen:Prof. Dr. Irmgard Sinning / Dr. Gert BangeHeidelberg University Biochemistry Centerphone: +49 6221 54-4780e-mail: irmi.sinning(at)bzh.uni-heidelberg.de/ gert.bange(at)bzh.uni-heidelberg.de