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Structural basis of solute and signal transport across membranes

English title Structural basis of solute and signal transport across membranes
Applicant Engel Andreas
Number 108299
Funding scheme Project funding (Div. I-III)
Research institution M.E. Müller-Inst. Mikroskop & Strukturbiol. Biozentrum Universität Basel
Institution of higher education University of Basel - BS
Main discipline Structural Research
Start/End 01.10.2005 - 30.09.2011
Approved amount 1'454'000.00
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All Disciplines (3)

Discipline
Structural Research
Biophysics
Biochemistry

Keywords (6)

membrane proteins; membrane protein expression; aquaporins; GPCRs; gated channels; electron crystallography

Lay Summary (English)

Lead
Lay summary
Membrane proteins are lipid bilayer-embedded nanomachines that fulfill key functions such as energy conversion, solute transport, secretion and signal transduction. 30% of all proteins are membrane bound, are related to many diseases and represent 70% of all drug targets. Progress in membrane protein structure determination is key to understand many cellular functions, and will provide information for new pharmaceutical therapies. Membrane proteins cannot often be purified from natural sources in the amounts required for structural analyses, and need to be overexpressed. Purification and stabilization of membrane proteins, which are fragile after extraction from the bilayer, is difficult and hinders progress in 3D crystallization and solution NMR. Reconstitution of membrane proteins into 2D crystals in the presence of lipids restores the native environment of membrane proteins as well as their biological activity. Electron crystallography and atomic force microscopy (AFM) are used to study the atomic structure and the function-related dynamics of native membrane proteins in such 2D crystals.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Reference-Free Alignment and Sorting of Single-Molecule Force Spectroscopy Data
Bosshart PD, Frederix PLTM, Engel A (2012), Reference-Free Alignment and Sorting of Single-Molecule Force Spectroscopy Data, in BIOPHYSICAL JOURNAL, 102(9), 2202-2211.
Reconstitution of water channel function and 2D-crystallization of human aquaporin 8
Agemark M, Kowal J, Kukulski W, Norden K, Gustavsson N, Johanson U, Engel A, Kjellbom P (2012), Reconstitution of water channel function and 2D-crystallization of human aquaporin 8, in BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 1818(3), 839-850.
Connecting mu-fluidics to electron microscopy
Kemmerling S, Ziegler J, Schweighauser G, Arnold SA, Giss D, Muller SA, Ringler P, Goldie KN, Goedecke N, Hierlemann A, Stahlberg H, Engel A, Braun T (2012), Connecting mu-fluidics to electron microscopy, in JOURNAL OF STRUCTURAL BIOLOGY, 177(1), 128-134.
Looking back at a quarter-century of research at the Maurice E. Muller Institute for Structural Biology
Muller SA, Engel A (2012), Looking back at a quarter-century of research at the Maurice E. Muller Institute for Structural Biology, in JOURNAL OF STRUCTURAL BIOLOGY, 177(1), 3-13.
Optimizing the refolding conditions of self-assembling polypeptide nanoparticles that serve as repetitive antigen display systems
Yang YK, Ringler P, Muller SA, Burkhard P (2012), Optimizing the refolding conditions of self-assembling polypeptide nanoparticles that serve as repetitive antigen display systems, in JOURNAL OF STRUCTURAL BIOLOGY, 177(1), 168-176.
Rhodopsin-transducin heteropentamer: Three-dimensional structure and biochemical characterization
Jastrzebska B, Ringler P, Lodowski DT, Moiseenkova-Bell V, Golczak M, Muller SA, Palczewski K, Engel A (2011), Rhodopsin-transducin heteropentamer: Three-dimensional structure and biochemical characterization, in JOURNAL OF STRUCTURAL BIOLOGY, 176(3), 387-394.
Cloning, expression, purification, and characterization of the membrane protein UncI from Escherichia coli
Hartmann C, Engel A (2011), Cloning, expression, purification, and characterization of the membrane protein UncI from Escherichia coli, in PROTEIN EXPRESSION AND PURIFICATION, 79(2), 187-190.
The chlorosome of Chlorobaculum tepidum: Size, mass and protein composition revealed by electron microscopy, dynamic light scattering and mass spectrometry-driven proteomics
Kouyianou K, De Bock PJ, Muller SA, Nikolaki A, Rizos A, Krzyzanek V, Aktoudianaki A, Vandekerckhove J, Engel A, Gevaert K, Tsiotis G (2011), The chlorosome of Chlorobaculum tepidum: Size, mass and protein composition revealed by electron microscopy, dynamic light scattering and mass spectrometry-driven proteomics, in PROTEOMICS, 11(14), 2867-2880.
Simulation and correction of electron images of tilted planar weak-phase samples
Mariani V, Schenk AD, Philippsen A, Engel A (2011), Simulation and correction of electron images of tilted planar weak-phase samples, in JOURNAL OF STRUCTURAL BIOLOGY, 174(2), 259-268.
Simulation and correction of electron images of tilted planar weak-phase samples
Mariani V, Schenk AD, Philippsen A, Engel A (2011), Simulation and correction of electron images of tilted planar weak-phase samples, in JOURNAL OF STRUCTURAL BIOLOGY, 174(2), 259-268.
Assessing the structure and function of single biomolecules with scanning transmission electron and atomic force microscopes
Muller SA, Muller DJ, Engel A (2011), Assessing the structure and function of single biomolecules with scanning transmission electron and atomic force microscopes, in MICRON, 42(2), 186-195.
Automated screening of 2D crystallization trials using transmission electron microscopy: A high-throughput tool-chain for sample preparation and microscopic analysis
Coudray N, Hermann G, Caujolle-Bert D, Karathanou A, Erne-Brand F, Buessler JL, Daum P, Plitzko JM, Chami M, Mueller U, Kihl H, Urban JP, Engel A, Remigy HW (2011), Automated screening of 2D crystallization trials using transmission electron microscopy: A high-throughput tool-chain for sample preparation and microscopic analysis, in JOURNAL OF STRUCTURAL BIOLOGY, 173(2), 365-374.
Five challenges to bringing single-molecule force spectroscopy into living cells
Dufrene YF, Evans E, Engel A, Helenius J, Gaub HE, Muller DJ (2011), Five challenges to bringing single-molecule force spectroscopy into living cells, in NATURE METHODS, 8(2), 123-127.
A Structural Model for Apolipoprotein C-II Amyloid Fibrils: Experimental Characterization and Molecular Dynamics Simulations
Teoh CL, Pham CLL, Todorova N, Hung A, Lincoln CN, Lees E, Lam YH, Binger KJ, Thomson NH, Radford SE, Smith TA, Muller SA, Engel A, Griffin MDW, Yarovsky I, Gooley PR, Howlett GJ (2011), A Structural Model for Apolipoprotein C-II Amyloid Fibrils: Experimental Characterization and Molecular Dynamics Simulations, in JOURNAL OF MOLECULAR BIOLOGY, 405(5), 1246-1266.

Associated projects

Number Title Start Funding scheme
125110 Unravelling the structure of the Yersinia Ysc injectisome 01.07.2009 Sinergia
59415 Atomic Structure and function of Membrane channels, transporters and receptors 01.10.2000 Project funding (Div. I-III)

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