2I6W

Crystal structure of the multidrug efflux transporter AcrB

2I6W の概要

• エントリーDOI: 10.2210/pdb2i6w/pdb
• 分子名称: Acriflavine resistance protein B (1 entity in total)
• 機能のキーワード: membrane protein, multidrug efflux transporter, acrb, transport protein
• 由来する生物種: Escherichia coli
• 細胞内の位置: Cell inner membrane; Multi-pass membrane protein: P31224
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 113665.18

構造登録者

Das, D.,Xu, Q.S.,Kim, S.H. (登録日: 2006-08-29, 公開日: 2007-05-01, 最終更新日: 2024-02-21)

主引用文献

Das, D.,Xu, Q.S.,Lee, J.Y.,Ankoudinova, I.,Huang, C.,Lou, Y.,Degiovanni, A.,Kim, R.,Kim, S.H.
Crystal structure of the multidrug efflux transporter AcrB at 3.1A resolution reveals the N-terminal region with conserved amino acids.
J.Struct.Biol., 158:494-502, 2007

PubMed Abstract: 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 15 A as opposed to the previously reported value of approximately 30 A 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.

PubMed: 17275331
DOI: 10.1016/j.jsb.2006.12.004

実験手法

X-RAY DIFFRACTION (3.1 Å)