Molekulare Mechanismen der Destabilisierung und Fehlfaltung einzelner Membranproteine
Zusammenfassung der Projektergebnisse
Molecular interactions are the basic language of biological processes. They establish the forces interacting between the building blocks of proteins and other macromolecules, thus determining their functional roles. Because molecular interactions trigger virtually every biological process, approaches to decipher these interactions are needed. In this project proposal we have quantified inter- and intramolecular interactions that can lead to destabilization and malfunctional membrane proteins at physiological relevant conditions. We have also characterized the interactions that switch the functional state of membrane proteins. We have employed dynamic SMFS has been used to detect and characterize different types of molecular interactions that occur between and within native membrane proteins. The experiments detected and localized molecular interactions that stabilized membrane proteins, including how these interactions were established during folding of αhelical secondary structure elements into the native protein and how they changed with oligomerization, substrate binding, point mutations, and mutations. SMFS also enables investigators to detect and locate molecular interactions established during ligand and inhibitor binding. These exciting applications provide opportunities for studying the molecular forces of life. Further developments will elucidate the origins of molecular interactions encoded in their lifetimes, interaction ranges, interplay, and dynamics characteristic of biological systems.
Projektbezogene Publikationen (Auswahl)
- ‘Detecting molecular interactions that stabilize native bovine rhodopsin’. Journal of Molecular Biology (2006) 358, 255-269
K.T. Sapra, P.S.H. Park, A. Engel, S. Filipek, D.J. Müller & K. Palzcewski
- ‘Single-molecule studies of membrane proteins’. Current Opinion in Structural Biology (2006) 16, 489-495
D.J. Müller, K.T. Sapra, S. Scheuring, A. Kedrov, P.L. Frederix, D. Fotiadis, & A. Engel
- 'Deciphering molecular interactions of native membrane proteins by single-molecule force spectroscopy’. Annual Review of Biophysics and Biomolecular Structure (2007) 36, 233-260
A. Kedrov, H. Janovjak, K.T. Sapra & D.J. Müller
- ’Stabilizing effect of Zn2+ in native bovine rhodopsin’. Journal of Biological Chemistry (2007) 282, 11377-11385
P.S.-H. Park, K.T. Sapra, M. Koliński, S. Filipek, K. Palczewski & D.J. Müller
- ‘Mechanical properties of bovine rhodopsin and bacteriorhodopsin dictate energy landscape and guide conformational changes’. Langmuir (2008) 24, 1330-1337
K.T. Sapra, P.S.-H. Park, K. Palczewski & D.J. Müller
- ‘Point mutations of membrane protein alter energy landscape and unfolding pathways’. Journal of Molecular Biology (2008) 376, 1076-1090
K.T. Sapra, P. Balasubramanian, D. Labudde, J. Bowie & D.J. Müller
