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RESEARCH PRODUCT

Experiments Meet Hydrophobic Mismatch: A Re-evaluation Of The Orientation Of Model Transmembrane Peptides From Solid-State NMR

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The basic physical rules underlying the organization of biological membranes can be gathered under the simple, but powerful, concept of hydrophobic mismatch. For example, the mutual adjustment of the lipid and protein hydrophobic lengths can be related with the existence of lipid rafts and explain discrete secretory pathways in the Golgi apparatus. The orientation of membrane protein fragments is predicted to follow the same hydrophobic mismatch principles, as illustrated by some experiments and molecular dynamics simulations. However, this appears to be challenged by results of solid-state 2H NMR experiments on model transmembrane peptides, displaying tilt angle values unexpectedly small and weakly reacting to changes of the lipid bilayer thickness.Here we bridge theory and experiments to show that previous 2H NMR experimental data of model transmembrane peptides in membranes of different thickness can be re-interpreted by using alternative models which consider explicit rigid-body peptide fluctuations. The result is a new set of tilts which follows nicely the hydrophobic mismatch expectations, and is coherent with molecular dynamics simulations as well as with other mismatch studies conducted with natural protein fragments.