Membrane Proteins; Protein Structure Determination; Protein Function; Protein Folding; Nuclear Magnetic Resonance (NMR); Transport across Membranes; Membrane Protein Biogenesis; Protein Dynamics; Mitochondria; Outer Membrane; Protein Complexes
Raschle Thomas, Rios Flores Perla, Opitz Christian, Müller Daniel J, Hiller Sebastian (2016), Monitoring Backbone Hydrogen-Bond Formation in β-Barrel Membrane Protein Folding., in Angewandte Chemie (International ed. in English)
, 55(20), 5952-5.
Burmann Björn M, Hiller Sebastian (2015), Chaperones and chaperone-substrate complexes: Dynamic playgrounds for NMR spectroscopists., in Progress in nuclear magnetic resonance spectroscopy
, 86-87, 41-64.
Morgado Leonor, Zeth Kornelius, Burmann Björn M, Maier Timm, Hiller Sebastian (2015), Characterization of the insertase BamA in three different membrane mimetics by solution NMR spectroscopy., in Journal of biomolecular NMR
, 61(3-4), 333-45.
Maier Timm, Clantin Bernard, Gruss Fabian, Dewitte Frédérique, Delattre Anne-Sophie, Jacob-Dubuisson Françoise, Hiller Sebastian, Villeret Vincent (2015), Conserved Omp85 lid-lock structure and substrate recognition in FhaC., in Nature communications
, 6, 7452-7452.
Thoma Johannes, Burmann Björn M, Hiller Sebastian, Müller Daniel J (2015), Impact of holdase chaperones Skp and SurA on the folding of β-barrel outer-membrane proteins., in Nature structural & molecular biology
, 22(10), 795-802.
Gruss Fabian, Hiller Sebastian, Maier Timm (2015), Purification and Bicelle Crystallization for Structure Determination of the E. coli Outer Membrane Protein TamA., in Buchanan S Noinaj N (ed.), Springer, New York, 259-70.
Burmann Björn M, Holdbrook Daniel A, Callon Morgane, Bond Peter J, Hiller Sebastian (2015), Revisiting the interaction between the chaperone Skp and lipopolysaccharide., in Biophysical journal
, 108(6), 1516-26.
Callon Morgane, Burmann Björn M, Hiller Sebastian (2014), Structural mapping of a chaperone-substrate interaction surface., in Angew. Chem. Int. Engl.
, 53(20), 5069-72.
Schnarwiler Felix, Niemann Moritz, Doiron Nicholas, Harsman Anke, Käser Sandro, Mani Jan, Chanfon Astrid, Dewar Caroline E, Oeljeklaus Silke, Jackson Christopher B, Pusnik Mascha, Schmidt Oliver, Meisinger Chris, Hiller Sebastian, Warscheid Bettina, Schnaufer Achim C, Ochsenreiter Torsten, Schneider André (2014), Trypanosomal TAC40 constitutes a novel subclass of mitochondrial β-barrel proteins specialized in mitochondrial genome inheritance., in Proc. Natl. Acad. Sci. USA
, 111(21), 7624-9.
Burmann Björn M, Wang Congwei, Hiller Sebastian (2013), Conformation and dynamics of the periplasmic membrane-protein-chaperone complexes OmpX-Skp and tOmpA-Skp., in Nat. Struct. Mol. Biol.
, 20(11), 1265-72.
Hiller Sebastian (2013), The functional heart of the M2 channel., in Biophysical journal
, 104(8), 1639-40.
Gruss Fabian, Zähringer Franziska, Jakob Roman P, Burmann Björn M, Hiller Sebastian, Maier Timm (2013), The structural basis of autotransporter translocation by TamA., in Nat. Struct. Mol. Biol.
, 20(11), 1318-20.
Huber Matthias, Böckmann Anja, Hiller Sebastian, Meier Beat H (2012), 4D solid-state NMR for protein structure determination., in Physical chemistry chemical physics : PCCP
, 14(15), 5239-46.
Harsman Anke, Niemann Moritz, Pusnik Mascha, Schmidt Oliver, Burmann Björn M, Hiller Sebastian, Meisinger Chris, Schneider André, Wagner Richard (2012), Bacterial Origin of a Mitochondrial Outer Membrane Protein Translocase, in J. Biol. Chem.
, 287(37), 31437-45.
Yu Tsyr-Yan, Raschle Thomas, Hiller Sebastian, Wagner Gerhard (2012), Solution NMR spectroscopic characterization of human VDAC-2 in detergent micelles and lipid bilayer nanodiscs., in Biochimica et biophysica acta
, 1818(6), 1562-9.
Hiller Sebastian, Wagner Gerhard (2012), Solution NMR Spectroscopy of Integral Membrane Proteins, in Egelman E. (ed.), Elsevier, New York, 120-138.
Burmann Björn M, Hiller Sebastian (2012), Solution NMR studies of membrane-protein-chaperone complexes., in Chimia
, 66(10), 759-63.
Krähenbühl Barbara, Hiller Sebastian, Wider Gerhard (2011), 4D APSY-HBCB(CG)CDHD experiment for automated assignment of aromatic amino acid side chains in proteins., in Journal of biomolecular NMR
, 51(3), 313-8.
Gossert Alvar D, Hiller Sebastian, Fernandez Cesar (2010), Automated NMR Resonance Assignment of Large Proteins for Protein-Ligand Interaction Studies., in Journal of the American Chemical Society
, 133, 210-213.
Etzkorn Manuel, Zoonens Manuela, Catoire Laurent J, Popot Jean-Luc, Hiller Sebastian, How Amphipols Embed Membrane Proteins: Global Solvent Accessibility and Interaction with a Flexible Protein Terminus., in J. Membr. Biol.
Reckel Sina, Hiller Sebastian, Perspectives of solution NMR spectroscopy for structural and functional studies of integral membrane proteins, in Molecular Physics
One of the key goals in the current era of life sciences is the understanding of all cellular processes on a molecular level. Membrane proteins, which comprise about a third of typical proteomes, are responsible for a wide range of vital cellular functions, including signal transduction, catalysis, respiration, and transport. The function of a protein is dependent on its three-dimensional structure and whereas tens of thousands of high-resolution structures of soluble proteins have brought us tremendous biological insight over the past fifty years, with only 200 unique structures our knowledge of membrane proteins is still relatively sparse.The research of my group will contribute to our understanding of membrane proteins by studying the structures, functions and folding mechanisms of selected membrane proteins and their complexes at atomic resolution. We will mainly use solution nuclear magnetic resonance (NMR) spectroscopy, but also complementary techniques to answer our biological and biophysical questions. I propose three projects:A. One project is the structural biology of the translocase of the outer mitochondrial membrane (Tom), a multiprotein channel through which proteins are transported into the mitochondria. A large body of biochemical and biophysical data is available in the literature, including electron micrographs, but high-resolution three-dimensional structures of the Tom complex are unknown. We will determine the structure of Tom40, the core unit of the Tom complex by solution NMR spectroscopy. Then, we will study the structures of the transmembrane domains of the other Tom complex members and map their interaction sites with Tom40. The ultimate goal is a full biophysical model of the Tom complex and its substrate recognition mechanism. B. A second line of research aims at understanding fundamental biophysical principles of beta-barrel membrane protein folding. These proteins fold by a complex cooperative mechanism, which involves both a hydrophilic and a hydrophobic external phase. Using solution NMR spectroscopy with proton/deuterium exchange labeling, we want to characterize the in vitro folding mechanism of beta-barrel membrane proteins resolved for individual atomic sites. We also want to relate our studies to kinetic data on the single molecule level. Further, we will study mechanistic details of the chaperone assisted in vivo folding process and address the role of hydrophobic clusters in the unfolded states of soluble and membrane proteins. Our ultimate goal is to come up with a comprehensive description of the in vivo and in vitro folding mechanism of the beta-barrel integral membrane protein OmpX and related proteins.C. The development of groundbreaking NMR technology for structural and functional studies of proteins will be an integral part of the above projects. Such techniques will be applicable to membrane proteins but also stimulate NMR research on other proteins and their complexes. We will develop and improve isotope labeling schemes, NMR pulse sequences and high-resolution non-uniform sampling and processing schemes.