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Article: Structural contributions to the intracellular targeting strategies of antimicrobial peptides

TitleStructural contributions to the intracellular targeting strategies of antimicrobial peptides
Authors
KeywordsBuforin II
CD spectroscopy
DNA binding
Magainin 2
Peptide antibiotics
Pleurocidin
Issue Date2010
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/bbamem
Citation
Biochimica Et Biophysica Acta - Biomembranes, 2010, v. 1798 n. 10, p. 1934-1943 How to Cite?
AbstractThe interactions of cationic amphipathic antimicrobial peptides (AMPs) with anionic biological membranes have been the focus of much research aimed at improving the activity of such compounds in the search for therapeutic leads. However, many of these peptides are thought to have other polyanions, such as DNA or RNA, as their ultimate target. Here a combination of fluorescence and circular dichroism (CD) spectroscopies has been used to assess the structural properties of amidated versions of buforin II, pleurocidin and magainin 2 that support their varying abilities to translocate through bacterial membranes and bind to double stranded DNA. Unlike magainin 2 amide, a prototypical membrane disruptive AMP, buforin II amide adopts a poorly helical structure in membranes closely mimicking the composition of Gram negative bacteria, such as Escherichia coli, and binds to a short duplex DNA sequence with high affinity, ultimately forming peptide-DNA condensates. The binding affinities of the peptides to duplex DNA are shown to be related to the structural changes that they induce. Furthermore, CD also reveals the conformation of the bound peptide buforin II amide. In contrast with a synthetic peptide, designed to adopt a perfect amphipathic α-helix, buforin II amide adopts an extended or polyproline II conformation when bound to DNA. These results show that an α-helix structure is not required for the DNA binding and condensation activity of buforin II amide. © 2010 Elsevier B.V.
Persistent Identifierhttp://hdl.handle.net/10722/129338
ISSN
2015 Impact Factor: 3.687
2015 SCImago Journal Rankings: 1.769
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Medical Research Council
Wellcome Trust
University of London
Funding Information:

This work was supported by the Medical Research Council (NIRG to AJM), the Wellcome Trust (VIP Award to AJM and Capital Award for the KCL Centre for Biomolecular Spectroscopy), the University of London Central Research Fund (AR/CRF/B) and Applied Photophysics. We are grateful to Drs K.D. Bruce and T. Spasenovski for their assistance in setting up antibacterial testing in the Molecular Microbiology Research Laboratory (PSD).

References

 

DC FieldValueLanguage
dc.contributor.authorLan, Yen_HK
dc.contributor.authorYe, Yen_HK
dc.contributor.authorKozlowska, Jen_HK
dc.contributor.authorLam, JKWen_HK
dc.contributor.authorDrake, AFen_HK
dc.contributor.authorMason, AJen_HK
dc.date.accessioned2010-12-23T08:35:32Z-
dc.date.available2010-12-23T08:35:32Z-
dc.date.issued2010en_HK
dc.identifier.citationBiochimica Et Biophysica Acta - Biomembranes, 2010, v. 1798 n. 10, p. 1934-1943en_HK
dc.identifier.issn0005-2736en_HK
dc.identifier.urihttp://hdl.handle.net/10722/129338-
dc.description.abstractThe interactions of cationic amphipathic antimicrobial peptides (AMPs) with anionic biological membranes have been the focus of much research aimed at improving the activity of such compounds in the search for therapeutic leads. However, many of these peptides are thought to have other polyanions, such as DNA or RNA, as their ultimate target. Here a combination of fluorescence and circular dichroism (CD) spectroscopies has been used to assess the structural properties of amidated versions of buforin II, pleurocidin and magainin 2 that support their varying abilities to translocate through bacterial membranes and bind to double stranded DNA. Unlike magainin 2 amide, a prototypical membrane disruptive AMP, buforin II amide adopts a poorly helical structure in membranes closely mimicking the composition of Gram negative bacteria, such as Escherichia coli, and binds to a short duplex DNA sequence with high affinity, ultimately forming peptide-DNA condensates. The binding affinities of the peptides to duplex DNA are shown to be related to the structural changes that they induce. Furthermore, CD also reveals the conformation of the bound peptide buforin II amide. In contrast with a synthetic peptide, designed to adopt a perfect amphipathic α-helix, buforin II amide adopts an extended or polyproline II conformation when bound to DNA. These results show that an α-helix structure is not required for the DNA binding and condensation activity of buforin II amide. © 2010 Elsevier B.V.en_HK
dc.languageengen_US
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/bbamemen_HK
dc.relation.ispartofBiochimica et Biophysica Acta - Biomembranesen_HK
dc.subjectBuforin IIen_HK
dc.subjectCD spectroscopyen_HK
dc.subjectDNA bindingen_HK
dc.subjectMagainin 2en_HK
dc.subjectPeptide antibioticsen_HK
dc.subjectPleurocidinen_HK
dc.subject.meshAmides - chemistry-
dc.subject.meshAmino Acid Sequence-
dc.subject.meshAntimicrobial Cationic Peptides - chemistry - metabolism - pharmacology-
dc.subject.meshDNA, Bacterial - chemistry - metabolism-
dc.subject.meshPeptides - chemistry - metabolism - pharmacology-
dc.titleStructural contributions to the intracellular targeting strategies of antimicrobial peptidesen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0006-3002&volume=1798&issue=10&spage=1934&epage=1943&date=2010&atitle=Structural+contributions+to+the+intracellular+targeting+strategy+of+antimicrobial+peptides-
dc.identifier.emailLam, JKW: jkwlam@hku.hken_HK
dc.identifier.authorityLam, JKW=rp01346en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.bbamem.2010.07.003en_HK
dc.identifier.pmid20637722-
dc.identifier.pmcidPMC3309561-
dc.identifier.scopuseid_2-s2.0-77955655670en_HK
dc.identifier.hkuros176473en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77955655670&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume1798en_HK
dc.identifier.issue10en_HK
dc.identifier.spage1934en_HK
dc.identifier.epage1943en_HK
dc.identifier.isiWOS:000281920400010-
dc.publisher.placeNetherlandsen_HK
dc.identifier.scopusauthoridLan, Y=36159603200en_HK
dc.identifier.scopusauthoridYe, Y=36674233900en_HK
dc.identifier.scopusauthoridKozlowska, J=36673254100en_HK
dc.identifier.scopusauthoridLam, JKW=8404243000en_HK
dc.identifier.scopusauthoridDrake, AF=7103355364en_HK
dc.identifier.scopusauthoridMason, AJ=8861864900en_HK
dc.identifier.citeulike7590581-

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