Max-Planck Institute for Molecular Physiology, Dortmund, Germany
Institute of Biochemistry and Molecular Biology II, Heinrich-Heine University Medical Center, Düsseldorf, Germany
Proteins point mutations belong to the biological variations that are indispensable driving force of evolution. They play a significant role in the adaptation of organisms to the changing environment or in the micro-evolution of immune system. However, they are in the focus of interest predominately because of their harmful potency. Occurring during the life can lead to various diseases and cancer with possible lethal consequences. Inherited via the germline can be also lethal or cause live-long handicaps. Although many cases are known, mechanism by which the point mutations influence the functions of proteins is vastly unknown. Moreover, general question arises: “Is there some general mechanism at all?”
In several studies we have investigated the impact of single or multiple point mutations on protein functions, most recently on the function of key GTPase Ras. Nevertheless either at molecular or cellular level, under in‑vivo or in‑vitro conditions, with natural or artificial mutations – results indicate that the issue is much harder then anticipated.
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2. Cirstea, I.C., Kutsche, K., Dvorsky, R., Gremer, L., Carta, C., Horn, D., Roberts, A.E., Lepri, F., Merbitz-Zahradnik, T., König, R., Kratz, C.P., Pantaleoni, F., Dentici, M.L., Joshi, V.A., Kucherlapati, R.S., Mazzanti, L., Mundlos, S., Patton, M.A., Silenko, M.C., Rossi, C., Zadino, G., Digilio, C., Stuppia, L., Seemanova, E., Pennacchio, L.A., Gelb, B.D., Dallapiccola, B., Wittinghofer, A., Ahmadian, M.R., Tartaglia, M., Zenker, M. A restricted spectrum of NRAS mutations causes Noonan syndrome. Nat Genet. 42, (2010), 27-29.
3. Gremer, L., Merbitz-Zahradnik, T., Dvorsky, R., Cirstea, I.C., Kratz, C.P., Zenker, M., Wittinghofer, A., Ahmadian, M.R. Germline KRAS mutations cause aberrant biochemical and physical properties leading to developmental disorders. Hum Mutat. 32, (2011), 33-43.