N-terminal aromatic residues closely impact the cytolytic activity of cupiennin 1a, a major spider venom peptide

Kuhn-Nentwig, Lucia Gerda; Sheynis, Tania; Kolusheva, Sofiya; Nentwig, Wolfgang (2013). N-terminal aromatic residues closely impact the cytolytic activity of cupiennin 1a, a major spider venom peptide. Toxicon, 75, pp. 177-186. Elsevier 10.1016/j.toxicon.2013.03.003

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Cupiennins are small cationic a-helical peptides from the venom of the ctenid spider Cupiennius salei which are characterized by high bactericidal as well as hemolytic activities. To gain insight into the determinants responsible for the broad cytolytic activities, two analogues of cupiennin 1a with different N-terminal hydrophobicities were designed. The insecticidal, bactericidal and hemolytic activities of these analogues were assayed and compared to the native peptide. Specifically, substitution of two N-terminal Phe residues by Ala results in less pronounced insecticidal and cytolytic activity, whereas a substitution by Lys reduces strongly its bactericidal activity and completely diminishes its hemolytic activity up to very high tested concentrations. Biophysical analyses of peptide/bilayer membrane interactions point to distinct interactions of the analogues with lipid bilayers, and dependence upon membrane surface charge. Indeed, we find that lower hemolytic activity was correlated with less surface association of the analogues. In contrast, our data indicate that the reduced bactericidal activity of the two cupiennin 1a analogues likely correspond to greater bilayer-surface localization of the peptides. Overall, ultimate insertion and destruction of the host cell membrane is highly dependent on the presence of Phe-2 and Phe-6 (Cu 1a) or Leu-6 (Cu 2a) in the N-terminal sequences of native cupiennins.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Ecology and Evolution (IEE) > Community Ecology
08 Faculty of Science > Department of Biology > Institute of Ecology and Evolution (IEE)

UniBE Contributor:

Kuhn-Nentwig, Lucia Gerda and Nentwig, Wolfgang

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 590 Animals (Zoology)
500 Science > 580 Plants (Botany)

ISSN:

0041-0101

Publisher:

Elsevier

Language:

English

Submitter:

Alexander Strauss

Date Deposited:

12 Apr 2014 10:43

Last Modified:

05 Dec 2014 04:03

Publisher DOI:

10.1016/j.toxicon.2013.03.003

BORIS DOI:

10.7892/boris.47451

URI:

https://boris.unibe.ch/id/eprint/47451

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