Membrane binding and oligomer formation by the calcium-dependent lipopeptide antibiotic A54145: a quantitative study with pyrene excimer fluorescence
| dc.contributor.author | Zhang, TianHua | |
| dc.contributor.author | Taylor, Scott D. | |
| dc.contributor.author | Palmer, Michael | |
| dc.contributor.author | Duhamel, Jean | |
| dc.date.accessioned | 2017-04-21T19:21:48Z | |
| dc.date.available | 2017-04-21T19:21:48Z | |
| dc.date.issued | 2016-09-20 | |
| dc.description | The final publication is available at Elsevier via http://doi.org/10.1016/j.bpj.2016.07.018 © 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | en |
| dc.description.abstract | A54145 is a lipopeptide antibiotic related to daptomycin that permeabilizes bacterial cell membranes. Its action requires both calcium and phosphatidylglycerol in the target membrane, and it is accompanied by the formation of membrane-associated oligomers. We here probed the interaction of A54145 with model membranes composed of dimyristoylphosphatidylcholine and dimyristoylphosphatidylglycerol, using the steady-state and time-resolved fluorescence of a pyrene-labeled derivative (Py-A54145). In solution, the labeled peptide was found to exist as a monomer. Its membrane interaction occurred in two stages that could be clearly distinguished by varying the calcium concentration. In the first stage, which was observed between 0.15 and 1 mM calcium, Py-A54145 bound to the membrane, as indicated by a strong increase in pyrene monomer emission. At the same calcium concentration, excimer emission increased also, suggesting that Py-A54145 had oligomerized. A global analysis of the time-resolved pyrene monomer and excimer fluorescence confirmed that Py-A54145 forms oligomers quantitatively and concomitantly with membrane binding. When calcium was raised beyond 1 mM, a distinct second transition was observed that may correspond to a doubling of the number of oligomer subunits. The collective findings confirm and extend our understanding of the action mode of A54145 and daptomycin. | en |
| dc.description.sponsorship | This work was supported by the Natural Sciences and Engineering Research Council of Canada operating grants to J.D. (201603-2013), M.P. (250265-2013), and S.T. (155283-2012). | en |
| dc.identifier.uri | https://doi.org/10.1016/j.bpj.2016.07.018 | |
| dc.identifier.uri | http://hdl.handle.net/10012/11715 | |
| dc.language.iso | en | en |
| dc.publisher | Elsevier | en |
| dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | * |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
| dc.subject | Excimer fluorescence | en |
| dc.subject | Solvent polarities | en |
| dc.subject | Py Scale | en |
| dc.subject | Daptomycin | en |
| dc.subject | Polymer | en |
| dc.subject | Model | en |
| dc.subject | Macromolecules | en |
| dc.subject | Association | en |
| dc.subject | Transitions | en |
| dc.subject | Inhibition | en |
| dc.title | Membrane binding and oligomer formation by the calcium-dependent lipopeptide antibiotic A54145: a quantitative study with pyrene excimer fluorescence | en |
| dc.type | Article | en |
| dcterms.bibliographicCitation | Zhang, T., Taylor, S. D., Palmer, M., & Duhamel, J. (2016). Membrane Binding and Oligomerization of the Lipopeptide A54145 Studied by Pyrene Fluorescence. Biophysical Journal, 111(6), 1267–1277. https://doi.org/10.1016/j.bpj.2016.07.018 | en |
| uws.contributor.affiliation1 | Faculty of Science | en |
| uws.contributor.affiliation2 | Chemistry | en |
| uws.peerReviewStatus | Reviewed | en |
| uws.scholarLevel | Faculty | en |
| uws.typeOfResource | Text | en |