Intermolecular Detergent-Membrane Protein NOEs for the Characterization of the Dynamics of Membrane Protein-Detergent Complexes

Author(s)
C. Eichmann, J. Orts, C. Tzitzilonis, B. Vogeli, S. Smrt, J. Lorieau, R. Riek
Abstract

The interaction between membrane proteins and lipids or lipid mimetics such as detergents is key for the three-dimensional structure and dynamics of membrane proteins. In NMR-based structural studies of membrane proteins, qualitative analysis of intermolecular nuclear Overhauser enhancements (NOEs) or paramagnetic resonance enhancement are used in general to identify the transmembrane segments of a membrane protein. Here, we employed a quantitative characterization of intermolecular NOEs between 1H of the detergent and 1HN of 2H-perdeuterated, 15N-labeled α-helical membrane protein–detergent complexes following the exact NOE (eNOE) approach. Structural considerations suggest that these intermolecular NOEs should show a helical-wheel-type behavior along a transmembrane helix or a membrane-attached helix within a membrane protein as experimentally demonstrated for the complete influenza hemagglutinin fusion domain HAfp23. The partial absence of such a NOE pattern along the amino acid sequence as shown for a truncated variant of HAfp23 and for the Escherichia coli inner membrane protein YidH indicates the presence of large tertiary structure fluctuations such as an opening between helices or the presence of large rotational dynamics of the helices. Detergent–protein NOEs thus appear to be a straightforward probe for a qualitative characterization of structural and dynamical properties of membrane proteins embedded in detergent micelles.

Organisation(s)
External organisation(s)
Eidgenössische Technische Hochschule Zürich, The Salk Institute for Biological Studies, University of Illinois at Chicago
Journal
The Journal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces & Biophysical
Volume
118
Pages
14288-14301
No. of pages
14
ISSN
1520-6106
DOI
https://doi.org/10.1021/jp509137q
Publication date
12-2014
Peer reviewed
Yes
Austrian Fields of Science 2012
106006 Biophysics, 106002 Biochemistry
Keywords
ASJC Scopus subject areas
Materials Chemistry, Surfaces, Coatings and Films, Physical and Theoretical Chemistry
Portal url
https://ucrisportal.univie.ac.at/en/publications/e9171cdb-1fdb-4dbd-9c33-3c9d8959c6ee