Importance of residue 13 and the C-terminus for the structure and activity of the antimicrobial peptide aurein 2.2

John T.J. Cheng, John D. Hale, Jason Kindrachuk, Havard Jessen, Melissa Elliott, Robert Hancock, Suzana K. Straus

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Previous studies on aurein 2.2 and 2.3 in DMPC/DMPG and POPC/POPG membranes have shown that bilayer thickness and phosphatidylglycerol content have a significant impact on the interaction of these peptides with membrane bilayers. Further examination with the DiSC35 assay has indicated that aurein 2.2 induces greater membrane leakage than aurein 2.3 in Staphylococcus aureus C622. The only difference between these peptides is a Leu to Ile mutation at residue 13. To better understand the importance of this residue, the structure and activity of the L13A, L13F, and L13V mutants were investigated. In addition, we investigated a number of peptides with truncations at the C-terminus to determine whether the C-terminus, which contains residue 13, is crucial for antimicrobial activity. Solution circular dichroism results demonstrated that the L13F mutation and the truncation of the C-terminus by six residues resulted in decreased helical content, whereas the L13A or L13V mutation and the truncation of the C-terminus by three residues showed little to no effect on the structure. Oriented circular dichroism results demonstrated that only an extensive C-terminal truncation reduced the ability of the peptide to insert into lipid bilayers. 31P NMR spectroscopy showed that all peptides disorder the headgroups. The implications of these results in terms of antimicrobial activity and the ability of these peptides to induce leakage in S. aureus are discussed. The results suggest that the presence of the 13th residue in aurein 2.2 is important for structure and activity, but the exact nature of residue 13 is less important as long as it is a hydrophobic residue.

LanguageEnglish
Pages2926-2935
Number of pages10
JournalBiophysical Journal
Volume99
Issue number9
DOIs
Publication statusPublished - 3 Nov 2010
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics

Cite this

Cheng, John T.J. ; Hale, John D. ; Kindrachuk, Jason ; Jessen, Havard ; Elliott, Melissa ; Hancock, Robert ; Straus, Suzana K. / Importance of residue 13 and the C-terminus for the structure and activity of the antimicrobial peptide aurein 2.2. In: Biophysical Journal. 2010 ; Vol. 99, No. 9. pp. 2926-2935.
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Importance of residue 13 and the C-terminus for the structure and activity of the antimicrobial peptide aurein 2.2. / Cheng, John T.J.; Hale, John D.; Kindrachuk, Jason; Jessen, Havard; Elliott, Melissa; Hancock, Robert; Straus, Suzana K.

In: Biophysical Journal, Vol. 99, No. 9, 03.11.2010, p. 2926-2935.

Research output: Contribution to journalArticle

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AU - Cheng, John T.J.

AU - Hale, John D.

AU - Kindrachuk, Jason

AU - Jessen, Havard

AU - Elliott, Melissa

AU - Hancock, Robert

AU - Straus, Suzana K.

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