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What vibrations tell us about GTPases

  • Carsten Kötting

    Carsten Kötting obtained a PhD in physical organic chemistry from the chemistry department of Ruhr-University Bochum, Germany in 1999, working on matrix isolation of organic intermediates. Afterwards he joined as a Feodor Lynen fellow the Zewail group at Caltech, were he did femtochemistry of organic intermediates. After two years he returned to Ruhr-University but joined the biophysics institute of Klaus Gerwert. He finished his habilitation in chemical biology working on time resolved FTIR spectroscopy of GTPases in 2009. His current research interests include besides the details of the reaction mechanisms of GTPases, the extension of vibrational spectroscopy to larger systems using Raman microscopy and the development of chemically modified surfaces for protein immobilization on ATR crystals.

     EMAIL logo     und Klaus Gerwert

    Klaus Gerwert is head of the Department of Biophysics at RUB. He is internationally recognized for his contributions in protein-dynamics with very high spatiotemporal resolution using a combination of time-resolved vibrational spectroscopy (FTIR and Raman) and biomolecular simulations (QM/MM). He elaborated the role of proteinbound water molecules in proton-transfer in proteins, especially in microbial rhodopsins like bacteriorhodopsin and channelrhodopsin. Furthermore, he contributed to the detailed understanding of the catalysis of G-proteins by their respective G-activating proteins like Ras and Rab. Recently his approach is extended to markerfree vibrational imaging in cells and tissue for their application in diagnostics. K. Gerwert graduated in biophysical chemistry (Freiburg 1985), was research scientist at the Max-Planck-Institute Dortmund (1986–1989), became Heisenberg-fellow at Scripps, USA, and MPI Dortmund (1990–1993). Since 1993 he is a full professor at the Ruhr-University Bochum (chair of biophysics). Since 2004 spokesman of SFB642 and since 2010 of PURE. Since 2009 Max-Planck fellow at the Max-Planck- CAS Partner-Institute in Shanghai (2009–2013 as director in a dual appointment). He received several awards and is a member of the NRW academy of science.

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Veröffentlicht/Copyright: 10. Januar 2015
Biological Chemistry
Aus der Zeitschrift Biological Chemistry Band 396 Heft 2

Abstract

In this review, we discuss how time-resolved Fourier transform infrared (FTIR) spectroscopy is used to understand how GTP hydrolysis is catalyzed by small GTPases and their cognate GTPase-activating proteins (GAPs). By interaction with small GTPases, GAPs regulate important signal transduction pathways and transport mechanisms in cells. The GTPase reaction terminates signaling and controls transport. Dysfunctions of GTP hydrolysis in these proteins are linked to serious diseases including cancer. Using FTIR, we resolved both the intrinsic and GAP-catalyzed GTPase reaction of the small GTPase Ras with high spatiotemporal resolution and atomic detail. This provided detailed insight into the order of events and how the active site is completed for catalysis. Comparisons of Ras with other small GTPases revealed conservation and variation in the catalytic mechanisms. The approach was extended to more nearly physiological conditions at a membrane. Interactions of membrane-anchored GTPases and their extraction from the membrane are studied using the attenuated total reflection (ATR) technique.

Keywords: biomolecular simulations; caged compounds; catalysis; proteins; reaction mechanism; vibrational spectroscopy
Corresponding authors: Carsten Kötting, Department of Biophysics, Ruhr University Bochum, Universitätsstr. 150, D-44801 Bochum, Germany, e-mail: ; and Klaus Gerwert: Department of Biophysics, Ruhr University Bochum, Universitätsstr. 150, D-44801 Bochum, Germany, e-mail:

About the authors

Carsten Kötting

Carsten Kötting obtained a PhD in physical organic chemistry from the chemistry department of Ruhr-University Bochum, Germany in 1999, working on matrix isolation of organic intermediates. Afterwards he joined as a Feodor Lynen fellow the Zewail group at Caltech, were he did femtochemistry of organic intermediates. After two years he returned to Ruhr-University but joined the biophysics institute of Klaus Gerwert. He finished his habilitation in chemical biology working on time resolved FTIR spectroscopy of GTPases in 2009. His current research interests include besides the details of the reaction mechanisms of GTPases, the extension of vibrational spectroscopy to larger systems using Raman microscopy and the development of chemically modified surfaces for protein immobilization on ATR crystals.

Klaus Gerwert

Klaus Gerwert is head of the Department of Biophysics at RUB. He is internationally recognized for his contributions in protein-dynamics with very high spatiotemporal resolution using a combination of time-resolved vibrational spectroscopy (FTIR and Raman) and biomolecular simulations (QM/MM). He elaborated the role of proteinbound water molecules in proton-transfer in proteins, especially in microbial rhodopsins like bacteriorhodopsin and channelrhodopsin. Furthermore, he contributed to the detailed understanding of the catalysis of G-proteins by their respective G-activating proteins like Ras and Rab. Recently his approach is extended to markerfree vibrational imaging in cells and tissue for their application in diagnostics. K. Gerwert graduated in biophysical chemistry (Freiburg 1985), was research scientist at the Max-Planck-Institute Dortmund (1986–1989), became Heisenberg-fellow at Scripps, USA, and MPI Dortmund (1990–1993). Since 1993 he is a full professor at the Ruhr-University Bochum (chair of biophysics). Since 2004 spokesman of SFB642 and since 2010 of PURE. Since 2009 Max-Planck fellow at the Max-Planck- CAS Partner-Institute in Shanghai (2009–2013 as director in a dual appointment). He received several awards and is a member of the NRW academy of science.

Acknowledgments

We acknowledge the Deutsche Forschungsgemeinschaft (grant no. SFB 642) for its financial support. We thank past and present members of the Bochum GTPase group and our collaborators for all their contributions and Konstantin Gavriljuk for manuscript proofreading. Special thanks are given to Roger S. Goody and Alfred Wittinghofer for an excellent and very fruitful collaboration over the years.

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Received: 2014-6-26
Accepted: 2014-7-29
Published Online: 2015-1-10
Published in Print: 2015-2-1

©2015 by De Gruyter

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https://doi.org/10.1515/hsz-2014-0219
Schlagwörter für diesen Artikel
biomolecular simulations; caged compounds; catalysis; proteins; reaction mechanism; vibrational spectroscopy

Artikel in diesem Heft

  1. Frontmatter
  2. Reviews
  3. Prokaryotic membrane vesicles: new insights on biogenesis and biological roles
  4. Cysteine cathepsins and cystatins: from ancillary tasks to prominent status in lung diseases
  5. What vibrations tell us about GTPases
  6. Minireview
  7. Optogenetics for gene expression in mammalian cells
  8. Research Articles/Short Communications
  9. Cell Biology and Signaling
  10. Mechanisms for proteinase-activated receptor 1-triggered prostaglandin E2 generation in mouse osteoblastic MC3T3-E1 cells
  11. Bone morphogenetic protein antagonist gremlin-1 regulates colon cancer progression
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