Structural and dynamic changes adopted by EmrE, multidrug transporter protein--Studies by molecular dynamics...

Area of Science:

• Biochemistry
• Molecular Biology
• Structural Biology

Background:

• EmrE protein confers bacterial multidrug resistance by exporting xenobiotics.
• It functions as a transporter, exchanging positively charged aromatic drugs for protons.
• Understanding EmrE's ligand recognition mechanism is crucial for combating antibiotic resistance.

Purpose of the Study:

• To investigate the molecular mechanisms of ligand recognition in the EmrE transporter.
• To explore the role of specific residues and conformational changes in substrate binding.
• To simulate the EmrE dimer and monomer within a phospholipid membrane environment.

Main Methods:

• Molecular dynamics simulations of EmrE monomer and dimer in a POPE+POPG membrane.
• Analysis of hydrogen bonds, including inter- and intra-molecular interactions.
• Assessment of water access, residue interactions, and conformational changes.

Main Results:

• Water access to transmembrane segments is regulated by aromatic/basic residues and helix dynamics.
• GLU14 in the apo-form is positioned for substrate interaction.
• Simulations suggest EmrE undergoes induced fit to accommodate ligands, with GLU14 binding positively charged fragments and aromatic residues binding non-polar parts.

Conclusions:

• EmrE's structure facilitates ligand binding through specific residue interactions (GLU14, TRP63, TYR40).
• The transporter exhibits induced fit capabilities for substrate accommodation.
• Simulation results support hypotheses regarding EmrE's conformational changes and function.