The Preference of Tryptophan for Membrane Interfaces

TLDR

Tryptophan and tyrosine residues preferentially locate at membrane interfaces, a phenomenon attributed to amphipathic interactions involving imino‑group hydrogen bonding and dipole forces. The study aimed to investigate the physical basis of tryptophan’s interfacial preference. This was achieved by applying 1H MAS, 2D NOESY, and solid‑state 2H NMR to probe four tryptophan analogues interacting with phosphatidylcholine membranes. The analogues positioned near the glycerol region produced only modest acyl‑chain perturbations, and reducing hydrogen‑bonding or dipole capacity did not enhance hydrocarbon penetration, thereby excluding simple amphipathic or dipolar mechanisms and indicating that the preference is governed mainly by tryptophan’s rigid, flat shape and aromatic π‑electron quadrupolar interactions at the interface.

Abstract

One of the ubiquitous features of membrane proteins is the preference of tryptophan and tyrosine residues for membrane surfaces that presumably arises from enhanced stability due to distinct interfacial interactions. The physical basis for this preference is widely believed to arise from amphipathic interactions related to imino group hydrogen bonding and/or dipole interactions. We have examined these and other possibilities for tryptophan's interfacial preference by using 1H magic angle spinning (MAS) chemical shift measurements, two-dimensional (2D) nuclear Overhauser effect spectroscopy (2D-NOESY) 1H MAS NMR, and solid state 2H NMR to study the interactions of four tryptophan analogues with phosphatidylcholine membranes. We find that the analogues reside in the vicinity of the glycerol group where they all cause similar modest changes in acyl chain organization and that hydrocarbon penetration was not increased by reduction of hydrogen bonding or electric dipole interaction ability. These observations rule out simple amphipathic or dipolar interactions as the physical basis for the interfacial preference. More likely, the preference is dominated by tryptophan's flat rigid shape that limits access to the hydrocarbon core and its π electronic structure and associated quadrupolar moment (aromaticity) that favor residing in the electrostatically complex interface environment.