Native Mass Spectrometry of Antimicrobial Peptides in Lipid Nanodiscs Elucidates Complex Assembly

Overview

Journal Anal Chem

Specialty Chemistry

Date 2019 Jun 29

PMID 31251560

Citations 28

Authors

Lawrence R Walker

Elaine M Marzluff

Julia A Townsend

William C Resager

Michael T Marty

Affiliations

Soon will be listed here.

Abstract

Antimicrobial peptides (AMPs) are generally cationic and amphipathic peptides that show potential applications to combat the growing threat of antibiotic resistant infections. AMPs are known to interact with bacterial membranes, but their mechanisms of toxicity and selectivity are poorly understood, in part because it is challenging to characterize AMP oligomeric complexes within lipid bilayers. Here, we used native mass spectrometry to measure the stoichiometry of AMPs inserted into lipoprotein nanodiscs with different lipid components. Titrations of increasing peptide concentration and collisional activation experiments reveal that AMPs can exhibit a range of behaviors from nonspecific incorporation into the nanodisc to formation of specific complexes. This new approach to characterizing formation of AMP complexes within lipid membranes will provide unique insights into AMP mechanisms.

Citing Articles

Native mass spectrometry prescreening of G protein-coupled receptor complexes for cryo-EM structure determination.

Kim D, Liu W, Viner R, Cherezov V Structure. 2024; 32(12):2206-2219.e4.

PMID: 39471802 PMC: 11625002. DOI: 10.1016/j.str.2024.10.004.

Deciphering Solution and Gas-Phase Interactions between Peptides and Lipids by Native Mass Spectrometry.

Kundlacz T, Schmidt C Anal Chem. 2023; 95(47):17292-17299.

PMID: 37956985 PMC: 10688224. DOI: 10.1021/acs.analchem.3c03428.

What's the defect? Using mass defects to study oligomerization of membrane proteins and peptides in nanodiscs with native mass spectrometry.

Townsend J, Marty M Methods. 2023; 218:1-13.

PMID: 37482149 PMC: 10529358. DOI: 10.1016/j.ymeth.2023.07.004.

Interspecies Variation Affects Islet Amyloid Polypeptide Membrane Binding.

Sanders H, Chalyavi F, Fields C, Kostelic M, Li M, Raleigh D J Am Soc Mass Spectrom. 2023; 34(6):986-990.

PMID: 37126782 PMC: 10330443. DOI: 10.1021/jasms.3c00005.

Investigating Daptomycin-Membrane Interactions Using Native MS and Fast Photochemical Oxidation of Peptides in Nanodiscs.

Reid D, Dash T, Wang Z, Aspinwall C, Marty M Anal Chem. 2023; 95(11):4984-4991.

PMID: 36888920 PMC: 10033427. DOI: 10.1021/acs.analchem.2c05222.

References

Patrick J, Gamez R, Russell D . The Influence of Lipid Bilayer Physicochemical Properties on Gramicidin A Conformer Preferences. Biophys J. 2016; 110(8):1826-1835. PMC: 4850349. DOI: 10.1016/j.bpj.2016.03.020. View

Leney A, Heck A . Native Mass Spectrometry: What is in the Name?. J Am Soc Mass Spectrom. 2016; 28(1):5-13. PMC: 5174146. DOI: 10.1007/s13361-016-1545-3. View

Keener J, Zambrano D, Zhang G, Zak C, Reid D, Deodhar B . Chemical Additives Enable Native Mass Spectrometry Measurement of Membrane Protein Oligomeric State within Intact Nanodiscs. J Am Chem Soc. 2018; 141(2):1054-1061. PMC: 6475481. DOI: 10.1021/jacs.8b11529. View

Joo H, Fu C, Otto M . Bacterial strategies of resistance to antimicrobial peptides. Philos Trans R Soc Lond B Biol Sci. 2016; 371(1695). PMC: 4874390. DOI: 10.1098/rstb.2015.0292. View

Bolla J, Agasid M, Mehmood S, Robinson C . Membrane Protein-Lipid Interactions Probed Using Mass Spectrometry. Annu Rev Biochem. 2019; 88:85-111. DOI: 10.1146/annurev-biochem-013118-111508. View

Seydlova G, Sokol A, Liskova P, Konopasek I, Fiser R . Daptomycin Pore Formation and Stoichiometry Depend on Membrane Potential of Target Membrane. Antimicrob Agents Chemother. 2018; 63(1). PMC: 6325215. DOI: 10.1128/AAC.01589-18. View

den Hertog A, van Marle J, van Veen H, Vant Hof W, Bolscher J, Veerman E . Candidacidal effects of two antimicrobial peptides: histatin 5 causes small membrane defects, but LL-37 causes massive disruption of the cell membrane. Biochem J. 2005; 388(Pt 2):689-95. PMC: 1138977. DOI: 10.1042/BJ20042099. View

Yang Z, Choi H, Weisshaar J . Melittin-Induced Permeabilization, Re-sealing, and Re-permeabilization of E. coli Membranes. Biophys J. 2018; 114(2):368-379. PMC: 5984949. DOI: 10.1016/j.bpj.2017.10.046. View

Patrick J, Zerfas B, Gao J, Russell D . Rapid capillary mixing experiments for the analysis of hydrophobic membrane complexes directly from aqueous lipid bilayer solutions. Analyst. 2016; 142(2):310-315. DOI: 10.1039/c6an02290a. View

10.

Guha S, Ghimire J, Wu E, Wimley W . Mechanistic Landscape of Membrane-Permeabilizing Peptides. Chem Rev. 2019; 119(9):6040-6085. PMC: 9235363. DOI: 10.1021/acs.chemrev.8b00520. View

11.

Calabrese A, Radford S . Mass spectrometry-enabled structural biology of membrane proteins. Methods. 2018; 147:187-205. DOI: 10.1016/j.ymeth.2018.02.020. View

12.

Veatch W, Stryer L . The dimeric nature of the gramicidin A transmembrane channel: conductance and fluorescence energy transfer studies of hybrid channels. J Mol Biol. 1977; 113(1):89-102. DOI: 10.1016/0022-2836(77)90042-0. View

13.

Ritchie T, Grinkova Y, Bayburt T, Denisov I, Zolnerciks J, Atkins W . Chapter 11 - Reconstitution of membrane proteins in phospholipid bilayer nanodiscs. Methods Enzymol. 2009; 464:211-31. PMC: 4196316. DOI: 10.1016/S0076-6879(09)64011-8. View

14.

Ulmschneider J, Ulmschneider M . Molecular Dynamics Simulations Are Redefining Our View of Peptides Interacting with Biological Membranes. Acc Chem Res. 2018; 51(5):1106-1116. DOI: 10.1021/acs.accounts.7b00613. View

15.

Marty M, Hoi K, Gault J, Robinson C . Probing the Lipid Annular Belt by Gas-Phase Dissociation of Membrane Proteins in Nanodiscs. Angew Chem Int Ed Engl. 2015; 55(2):550-4. PMC: 4736441. DOI: 10.1002/anie.201508289. View

16.

Yasir M, Willcox M, Dutta D . Action of Antimicrobial Peptides against Bacterial Biofilms. Materials (Basel). 2018; 11(12). PMC: 6317029. DOI: 10.3390/ma11122468. View

17.

Reid D, Keener J, Wheeler A, Zambrano D, Diesing J, Reinhardt-Szyba M . Engineering Nanodisc Scaffold Proteins for Native Mass Spectrometry. Anal Chem. 2017; 89(21):11189-11192. DOI: 10.1021/acs.analchem.7b03569. View

18.

Jamasbi E, Batinovic S, Sharples R, Sani M, Robins-Browne R, Wade J . Melittin peptides exhibit different activity on different cells and model membranes. Amino Acids. 2014; 46(12):2759-66. DOI: 10.1007/s00726-014-1833-9. View

19.

van de Waterbeemd M, Fort K, Boll D, Reinhardt-Szyba M, Routh A, Makarov A . High-fidelity mass analysis unveils heterogeneity in intact ribosomal particles. Nat Methods. 2017; 14(3):283-286. DOI: 10.1038/nmeth.4147. View

20.

Sancho-Vaello E, Francois P, Bonetti E, Lilie H, Finger S, Gil-Ortiz F . Structural remodeling and oligomerization of human cathelicidin on membranes suggest fibril-like structures as active species. Sci Rep. 2017; 7(1):15371. PMC: 5684418. DOI: 10.1038/s41598-017-14206-1. View