Publications
73 results found
Bountra K, Hagelueken G, Choudhury HG, et al., 2017, Structural basis for antibacterial peptide self-immunity by the bacterial ABC transporter McjD, The EMBO Journal, Vol: 36, Pages: 3062-3079, ISSN: 0261-4189
Certain pathogenic bacteria produce and release toxic peptides to ensure either nutrient availability or evasion from the immune system. These peptides are also toxic to the producing bacteria that utilize dedicated ABC transporters to provide self‐immunity. The ABC transporter McjD exports the antibacterial peptide MccJ25 in Escherichia coli. Our previously determined McjD structure provided some mechanistic insights into antibacterial peptide efflux. In this study, we have determined its structure in a novel conformation, apo inward‐occluded and a new nucleotide‐bound state, high‐energy outward‐occluded intermediate state, with a defined ligand binding cavity. Predictive cysteine cross‐linking in E. coli membranes and PELDOR measurements along the transport cycle indicate that McjD does not undergo major conformational changes as previously proposed for multi‐drug ABC exporters. Combined with transport assays and molecular dynamics simulations, we propose a novel mechanism for toxic peptide ABC exporters that only requires the transient opening of the cavity for release of the peptide. We propose that shielding of the cavity ensures that the transporter is available to export the newly synthesized peptides, preventing toxic‐level build‐up.
Qu F, Beis K, 2017, Structural studies of the AcrB transporter and inhibitor development, Publisher: INT UNION CRYSTALLOGRAPHY, Pages: C398-C398, ISSN: 2053-2733
Bountra K, Choudhury H, El Omari K, et al., 2017, Structural basis of antibacterial peptide self-immunity by ABC transporters, Publisher: INT UNION CRYSTALLOGRAPHY, Pages: C395-C395, ISSN: 2053-2733
Mehmood S, Corradi V, Choudhury HG, et al., 2016, Structural and functional basis for lipid synergy on the activity of the antibacterial peptide ABC transporter McjD, Journal of Biological Chemistry, Vol: 291, Pages: 21656-21668, ISSN: 1083-351X
The lipid bilayer is a dynamic environment that consists of a mixture of lipids with different properties that regulate the function of membrane proteins; these lipids are either annular, masking the protein hydrophobic surface, or specific lipids, essential for protein function. In this study, using tandem mass spectrometry, we have identified specific lipids associated with the Escherichia coli ABC transporter McjD, which translocates the antibacterial peptide MccJ25. Using non-denaturing mass spectrometry, we show that McjD in complex with MccJ25 survives the gas-phase. Partial delipidation of McjD resulted in reduced ATPase activity and thermostability as shown by Circular Dichroism, both of which could be restored upon addition of defined E. coli lipids. We have resolved a phosphatidylglycerol lipid associated with McjD at 3.4 Å resolution, while molecular dynamic simulations carried out in different lipid environments assessed the binding of specific lipids to McjD. Combined, our data show a synergistic effect of zwitterionic and negatively charged lipids on the activity of McjD; the zwitterionic lipids provide structural stability to McjD whereas the negatively charged lipids are essential for its function.
Beis K, 2015, Structural basis for the mechanism of ABC transporters, BIOCHEMICAL SOCIETY TRANSACTIONS, Vol: 43, Pages: 889-893, ISSN: 0300-5127
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- Citations: 129
Gu R-X, Corradi V, Singh G, et al., 2015, Conformational Changes of the Antibacterial Peptide ATP Binding Cassette Transporter McjD Revealed by Molecular Dynamics Simulations, BIOCHEMISTRY, Vol: 54, Pages: 5989-5998, ISSN: 0006-2960
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- Citations: 19
Axford D, Foadi J, Hu N-J, et al., 2015, Structure determination of an integral membrane protein at room temperature from crystals <i>in situ</i>, ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, Vol: 71, Pages: 1228-1237, ISSN: 2059-7983
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- Citations: 35
Gu R-X, Corradi V, Singh G, et al., 2015, Conformational Changes of the ABC Transporter McjD Revealed by Molecular Dynamics Simulations, BIOPHYSICAL JOURNAL, Vol: 108, Pages: 89A-89A, ISSN: 0006-3495
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- Citations: 1
Lee C, Kang HJ, Hjelm A, et al., 2014, MemStar: A one-shot <i>Escherichia coli</i>-based approach for high-level bacterial membrane protein production, FEBS LETTERS, Vol: 588, Pages: 3761-3769, ISSN: 0014-5793
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- Citations: 21
Choudhury HG, Tong Z, Mathavan I, et al., 2014, Structure of an antibacterial peptide ATP-binding cassette transporter in a novel outward occluded state, Proceedings of the National Academy of Sciences of the United States of America, Vol: 111, Pages: 9145-9150, ISSN: 0027-8424
Enterobacteriaceae produce antimicrobial peptides for survival under nutrient starvation. Microcin J25 (MccJ25) is an antimicrobial peptide with a unique lasso topology. It is secreted by the ATP-binding cassette (ABC) exporter McjD, which ensures self-immunity of the producing strain through efficient export of the toxic mature peptide from the cell. Here we have determined the crystal structure of McjD from Escherichia coli at 2.7-Å resolution, which is to the authors’ knowledge the first structure of an antibacterial peptide ABC transporter. Our functional and biochemical analyses demonstrate McjD-dependent immunity to MccJ25 through efflux of the peptide. McjD can directly bind MccJ25 and displays a basal ATPase activity that is stimulated by MccJ25 in both detergent solution and proteoliposomes. McjD adopts a new conformation, termed nucleotide-bound outward occluded. The new conformation defines a clear cavity; mutagenesis and ligand binding studies of the cavity have identified Phe86, Asn134, and Asn302 as important for recognition of MccJ25. Comparisons with the inward-open MsbA and outward-open Sav1866 structures show that McjD has structural similarities with both states without the intertwining of transmembrane (TM) helices. The occluded state is formed by rotation of TMs 1 and 2 toward the equivalent TMs of the opposite monomer, unlike Sav1866 where they intertwine with TMs 3–6 of the opposite monomer. Cysteine cross-linking studies on the McjD dimer in inside-out membrane vesicles of E. coli confirmed the presence of the occluded state. We therefore propose that the outward-occluded state represents a transition intermediate between the outward-open and inward-open conformation of ABC exporters.
Mathavan I, Zirah S, Mehmood S, et al., 2014, Structural basis for hijacking siderophore receptors by antimicrobial lasso peptides, Nature Chemical Biology, Vol: 10, Pages: 340-342, ISSN: 1552-4450
The lasso peptide microcin J25 is known to hijack the siderophore receptor FhuA for initiating internalization. Here, we provide what is to our knowledge the first structural evidence on the recognition mechanism, and our biochemical data show that another closely related lasso peptide cannot interact with FhuA. Our work provides an explanation on the narrow activity spectrum of lasso peptides and opens the path to the development of new antibacterials.
Bountra K, Choudhury H, El Omari K, et al., 2014, Structural basis of antibacterial peptide self-immunity by ABC transporters, Publisher: INT UNION CRYSTALLOGRAPHY, Pages: C395-C395, ISSN: 2053-2733
Qu F, Beis K, 2014, Structural studies of the AcrB transporter and inhibitor development, Publisher: INT UNION CRYSTALLOGRAPHY, Pages: C398-C398, ISSN: 2053-2733
Runti G, Ruiz MDCL, Stoilova T, et al., 2013, Functional Characterization of SbmA, a Bacterial Inner Membrane Transporter Required for Importing the Antimicrobial Peptide Bac7(1-35), JOURNAL OF BACTERIOLOGY, Vol: 195, Pages: 5343-5351, ISSN: 0021-9193
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- Citations: 74
Corbalan N, Runti G, Adler C, et al., 2013, Functional and Structural Study of the Dimeric Inner Membrane Protein SbmA, JOURNAL OF BACTERIOLOGY, Vol: 195, Pages: 5352-5361, ISSN: 0021-9193
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- Citations: 29
Choudhury HG, Beis K, 2013, The dimeric form of the unphosphorylated response regulator BaeR, PROTEIN SCIENCE, Vol: 22, Pages: 1287-1293, ISSN: 0961-8368
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- Citations: 11
Choudhury HG, Beis K, 2013, Tellurite-Resistance Protein TehA from Escherichia coli, Encyclopedia of Metalloproteins, Editors: Kretsinger, Uversky, Permyakov, Publisher: Springer, ISBN: 978-1-4614-1532-9
Choudhury HG, Beis K, 2013, Tellurite-Detoxifying Protein TehB from Escherichia coli, Encyclopedia of Metalloproteins, Editors: Kretsinger, Uversky, Permyakov, Publisher: Springer, ISBN: 978-1-4614-1532-9
Mathavan I, Beis K, 2012, The role of bacterial membrane proteins in the internalization of microcin MccJ25 and MccB17, Biochemical Society Transactions, Vol: 40, Pages: 1539-1543
Lou H, Chen M, Black SS, et al., 2011, Altered Antibiotic Transport in OmpC Mutants Isolated from a Series of Clinical Strains of Multi-Drug Resistant <i>E</i>. <i>coli</i>, PLOS ONE, Vol: 6, ISSN: 1932-6203
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- Citations: 84
Choudhury HG, Cameron AD, Iwata S, et al., 2011, <i>Escherichia coli</i> detoxification of chalcolgens by TehAB, 36th FEBS Congress of the Biochemistry for Tomorrows Medicine, Publisher: WILEY-BLACKWELL, Pages: 101-101, ISSN: 1742-464X
Choudhury HG, Cameron AD, Iwata S, et al., 2011, Structure and mechanism of the chalcogen-detoxifying protein TehB from <i>Escherichia coli</i>, BIOCHEMICAL JOURNAL, Vol: 435, Pages: 85-91, ISSN: 0264-6021
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- Citations: 12
Sonoda Y, Newstead S, Hu N-J, et al., 2011, Benchmarking Membrane Protein Detergent Stability for Improving Throughput of High-Resolution X-ray Structures, STRUCTURE, Vol: 19, Pages: 17-25, ISSN: 0969-2126
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- Citations: 114
Bushell SR, Lou H, Wallat GD, et al., 2010, Crystallization and preliminary diffraction analysis of Wzi, a member of the capsule export and assembly pathway in <i>Escherichia coli</i>, ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS, Vol: 66, Pages: 1621-1625
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- Citations: 8
Choudhury HG, Beis K, 2010, Crystallization and initial X-ray diffraction analysis of the tellurite-resistance <i>S</i>-adenosyl-l-methionine transferase protein TehB from <i>Escherichia coli</i>, ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS, Vol: 66, Pages: 1496-1499
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- Citations: 4
Beale J, Lee SY, Iwata S, et al., 2010, Structure of the aliphatic sulfonate-binding protein SsuA from <i>Escherichia coli</i>, ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS, Vol: 66, Pages: 391-396
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- Citations: 8
Lou HB, Beis K, Naismith JH, 2009, Bacterial Membrane Proteins: The New Soluble Proteins?, Membrane Protein Crystallization, Editors: Delucas, Publisher: Academic Pr, Pages: 269-297, ISBN: 9780123749871
This volume of Current Topics in Membranes focuses on Membrane Protein Crystallization, beginning with a review of past successes and general trends, then ...
Lou H, Beis K, Naismith JH, 2009, Bacterial Membrane Proteins: The New Soluble Proteins?, MEMBRANE PROTEIN CRYSTALLIZATION, Vol: 63, Pages: 269-297, ISSN: 1063-5823
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- Citations: 1
Carpenter EP, Beis K, Cameron AD, et al., 2008, Overcoming the challenges of membrane protein crystallography, CURRENT OPINION IN STRUCTURAL BIOLOGY, Vol: 18, Pages: 581-586, ISSN: 0959-440X
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- Citations: 307
Drew D, Klepsch MM, Newstead S, et al., 2008, The structure of the efflux pump AcrB in complex with bile acid, MOLECULAR MEMBRANE BIOLOGY, Vol: 25, Pages: 677-682, ISSN: 0968-7688
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- Citations: 52
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