Fluorinated aromatic amino acids distinguish cation-π interactions from membrane insertion

Abstract

Background: Peripheral membrane proteins can interact with zwitterionic phospholipid headgroups or lipid tails. Results: Incorporation of fluorinated Phe or Tyr differentiates side chain insertion from PC-cation-π complexes. Conclusion: Enhanced binding of a fluorinated protein implies side chain insertion; weakened binding represents a cation-π complex. Significance: Fluorinated Tyr or Phe incorporation can elucidate membrane binding modes.