2i6w

From Proteopedia

Revision as of 12:58, 23 January 2008

Crystal structure of the multidrug efflux transporter AcrB

Overview

Crystal structures of the bacterial multidrug transporter AcrB in R32 and, C2 space groups showing both symmetric and asymmetric trimeric assemblies, respectively, supplemented with biochemical investigations, have provided, most of the structural basis for a molecular level understanding of the, protein structure and mechanisms for substrate uptake and translocation, carried out by this 114-kDa inner membrane protein. They suggest that AcrB, captures ligands primarily from the periplasm. Substrates can also enter, the inner cavity of the transporter from the cytoplasm, but the exact, mechanism of this remains undefined. Analysis of the amino acid sequences, of AcrB and its homologs revealed the presence of conserved residues at, the N-terminus including two phenylalanines which may be exposed to the, cytoplasm. Any potential role that these conserved residues may play in, function has not been addressed by existing biochemical or structural, studies. Since phenylalanine residues elsewhere in the protein have been, implicated in ligand binding, we explored the structure of this N-terminal, region to investigate structural determinants near the cytoplasmic opening, that may mediate drug uptake. Our structure of AcrB in R32 space group, reveals an N-terminus loop, reducing the diameter of the central opening, to approximately 15A as opposed to the previously reported value of, approximately 30A for crystal structures in this space group with, disordered N-terminus. Recent structures of the AcrB in C2 space group, have revealed a helical conformation of this N-terminus but have not, discussed its possible implications. We present the crystal structure of, AcrB that reveals the structure of the N-terminus containing the conserved, residues. We hope that the structural information provides a structural, basis for others to design further biochemical investigation of the role, of this portion of AcrB in mediating cytoplasmic ligand discrimination and, uptake.

About this Structure

2I6W is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

Reference

Crystal structure of the multidrug efflux transporter AcrB at 3.1A resolution reveals the N-terminal region with conserved amino acids., Das D, Xu QS, Lee JY, Ankoudinova I, Huang C, Lou Y, Degiovanni A, Kim R, Kim SH, J Struct Biol. 2007 Jun;158(3):494-502. Epub 2006 Dec 24. PMID:17275331

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