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Characterization of the LSGGQ and H motifs from the Escherichia coli lipid A transporter MsbA. Biochemistry 2006 Oct 17;45(41):12539-46



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Scopus ID

2-s2.0-33750038243   26 Citations


ATP-binding cassette (ABC) transporters make up one of the largest superfamilies of proteins known and have been shown to transport substrates ranging from lipids and antibiotics to sugars and amino acids. The dysfunction of ABC transporters has been linked to human pathologies such as cystic fibrosis, hyperinsulinemia, and macular dystrophy. Several bacterial ABC transporters are also necessary for bacterial survival and transport of virulence factors in an infected host. MsbA is a 65 kDa protein that forms a functional homodimer consisting of two six-helix transmembrane domains and two approximately 250 amino acid nucleotide-binding domains (NBD). The NBDs contain several conserved regions such as the Walker A, LSGGQ, and H motif that bind directly to ATP and align it for hydrolysis. MsbA transports lipid A, its native substrate, across the inner membrane of Gram-negative bacteria. The loss or dysfunction of MsbA results in a toxic accumulation of lipid A inside the cell, leading to cell-membrane instability and cell death. Using site-directed spin labeling electron paramagnetic resonance spectroscopy, conserved motifs within the MsbA NBD have been evaluated for structure and dynamics upon substrate binding. It has been determined that the LSGGQ NBD consensus sequence is consistent with an alpha-helical conformation and that these residues maintain extensive tertiary contacts throughout hydrolysis. The dynamics of the LSGGQ and the H-motif region have been studied in the presence of ATP, ADP, and ATP plus vanadate to identify the residues that are directly affected by interactions with the substrate before, after, and during hydrolysis, respectively.

Author List

Buchaklian AH, Klug CS


Candice S. Klug PhD Professor in the Biophysics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

ATP-Binding Cassette Transporters
Adenosine Triphosphate
Amino Acid Motifs
Bacterial Proteins
Binding Sites
Consensus Sequence
Electron Spin Resonance Spectroscopy
Escherichia coli
Escherichia coli Proteins
Models, Molecular
Mutagenesis, Site-Directed
Protein Conformation
Recombinant Proteins
Spin Labels
jenkins-FCD Prod-466 5b81815b8b3d1f46bfec16512ed5f574613f59c5