INTERFACIAL TRYPTOPHAN RESIDUES - A ROLE FOR THE CATION-PI EFFECT?
Frederic Nicholas Rønne Petersen 1, Morten 
stergaard Jensen 2 and Claus Helix Nielsen 1*
1 Quantum Protein Center, Technical University of Denmark
2 MEMPHYS
* To whom correspondence should be addressed. E-mail: claus.nielsen{at}fysik.dtu.dk.
Submitted on February 25, 2005
Revised on April 1, 2005
Accepted on 11 August 2005
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Abstract |
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Integral membrane proteins are characterized by having a preference for aromatic residues, e.g., tryptophan (W), at the interface between the lipid bilayer core and the aqueous phase. The reason for this is not clear, but it seems that the preference is related to a complex interplay between steric and electrostatic forces. The flat rigid paddle-like structure of tryptophan, associated with a quadrupolar moment (aromaticity) arising from the pi-electron cloud of the indole, interacts primarily with moieties in the lipid headgroup region hardly penetrating into the bilayer core. We have studied the interaction between the nitrogen moiety of lipid molecule headgroups and the ð-electron distribution of gramicidin (gA) tryptophan residues (W9,W11,W13, and W15) using Molecular Dynamics (MD) simulations of gA embedded in two hydrated lipid bilayers composed of 1-palmitoyl-2-oleoylphosphatidylethanolamine (POPE) and 1-palmitoyl-2-oleoylphosphatidyl-choline (POPC), respectively. We use a force field model for tryptophan, in which polarizability is only implicit, but we believe that classical MD force fields are sufficient to capture the most prominent features of the cation-pi interaction. Our criteria for cation-pi interactions are based on distance and angular requirements and the results suggest that cation-pi interactions are relevant for W11PE,W13PE, and W15PE; and to some extent W11PC and W13PC. W9 does not seem to engage in cation-pi interactions, neither in POPE nor POPC. The criteria for the cation-pi effect are satisfied more often in POPE than in POPC, whereas the H-bonding ability between the indole donor and the carbonyl acceptor is similar in POPE and POPC. This suggests an increased affinity for lipids with ethanolamine headgroups to transmembrane proteins enriched in interfacial tryptophans.
Key Words:
anchoring residues, cation-pi interactions, interfacial tryptophans, lipid-protein interactions
