Role of sequence bias in the topology of the multidrug transporter EmrE.
EmrE is the prototype of small multidrug resistance transporters and has emerged as a model of membrane protein evolution. Analysis of the distances separating symmetry-related site-specific spin labels, correlation of topological sequence bias to C-terminal orientation, to membrane insertion efficiency, and to resistance to ethidium bromide collectively demonstrate that EmrE monomers adopt a parallel topology in the functional dimer. We propose a coupled insertion and assembly model for EmrE in which the favorable energetics of the parallel dimer interface override topological constraints arising from weak asymmetry in positive charge distribution.
McHaourab
Hassane S
HS
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37232-0615, USA. hassane.mchaourab@vanderbilt.edu
Mishra
Sanjay
S
Koteiche
Hanane A
HA
Amadi
Sepan H
SH
D017920:Antiporters / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D019281:Dimerization; D004578:Electron Spin Resonance Spectroscopy; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004996:Ethidium / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation
D017920:Antiporters; D029968:Escherichia coli Proteins; D049452:Green Fluorescent Proteins; C075436:EmrE protein, E coli; D004996:Ethidium