THE PREFERENCE OF TRYPTOPHAN FOR MEMBRANE INTERFACES

One of the ubiquitous features of membrane proteins is the preference of tryptophan and tyrosine residues for membrane surfaces that presuma bly arises from enhanced stability due to distinct interfacial interac tions. The physical basis for this preference is widely believed to ar ise from amphipathic interactions related to imino group hydrogen bond ing and/or dipole interactions. We have examined these and other possi bilities for tryptophan's interfacial preference by using H-1 magic an gle spinning (MAS) chemical shift measurements, two-dimensional (2D) n uclear Overhauser effect spectroscopy (2D-NOESY) H-1 MAS NMR, and soli d state H-2 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 mo dest changes in acyl chain organization and that hydrocarbon penetrati on was not increased by reduction of hydrogen bonding or electric dipo le interaction ability. These observations rule out simple amphipathic or dipolar interactions as the physical basis for the interfacial pre ference. More likely, the preference is dominated by tryptophan's flat rigid shape that limits access to the hydrocarbon core and its pi ele ctronic structure and associated quadrupolar moment (aromaticity) that favor residing in the electrostatically complex interface environment .