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Regular version of the site

Article

Probing the effect of membrane contents on transmembrane protein-protein interaction using solution NMR and computer simulations

Biochimica et Biophysica Acta - Biomembranes. 2018. Vol. 1860. No. 12. P. 2486-2498.
Bragin P., Kuznetsov A.S., Bocharova O., Volynsky P., Arseniev A., Efremov R.G., Mineev K.

The interaction between the elements of the secondary structure is the key process, determining the spatial structure and activity of a membrane protein. The transmembrane (TM) helix-helix interaction is known to be especially important for the function of so-called type I or bitopic membrane proteins, which have small TM domains, consisting of a single ⍺-helix. In turn, the parameters of membrane environment is an important factor, influencing the free energy and mode of TM protein-protein and helix-helix contacts. However, to the date the studies of the lipid-related effects on the free energy and structural mode of TM helix-helix interactions are represented mainly by the computer simulations, performed mostly in the coarse-grained regime, which definitely need to be verified experimentally. In the present work, we provide the approach to study the helix-helix interactions in the TM domains of membrane proteins in various lipid environment using solution NMR spectroscopy and phospholipid bicelles. The technique is based on the properties of bicelles to form particles with the size, depending on the lipid/detergent ratio. To implement the approach, we report the experimental parameters of "ideal bicelle" models for four kinds of zwitterionic phospholipids, which can be also used in other structural studies. We show that size of bicelles and type of the rim-forming detergent do not affect substantially the spatial structure and stability of the model TM dimer. On the other hand, the effect of the bilayer thickness on the free energy of the dimer is dramatic, while the structure of the protein is unchanged in various lipids with fatty chains having length from 12 to 18 carbon atoms. The obtained data is analyzed from the viewpoint of hydrophobic mismatch and lipophobic effects, and sheds light on the folding determinants of α-helical membrane proteins.