Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/92442
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Type: Journal article
Title: Structural Analysis of Calmodulin Binding by nNOS Inhibitory Amphibian Peptides
Author: Calabrese, A.
Bowie, J.
Pukala, T.
Citation: Biochemistry, 2015; 54(2):567-576
Publisher: American Chemical Society
Issue Date: 2015
ISSN: 0006-2960
1520-4995
Statement of
Responsibility: 
Antonio N. Calabrese, John H. Bowie and Tara L. Pukala
Abstract: Calmodulin (CaM) is a ubiquitous protein in nature and plays a regulatory role in numerous biological processes, including the upregulation of nitric oxide (NO) synthesis in vivo. Several peptides that prevent NO production by interacting with CaM have been isolated in the cutaneous secretions of Australian amphibians, and are thought to serve as a defense mechanism against predators. In this work, we probe the mechanism by which three of these peptides, namely, caerin 1.8, dahlein 5.6, and a synthetic modification of citropin 1.1, interact with CaM to inhibit NO signaling. Isothermal titration calorimetry was used to determine thermodynamic parameters of the binding interactions and revealed that all the peptides bind to CaM in a similar fashion, with the peptide encapsulated between the two lobes of CaM. Ion mobility-mass spectrometry was used to investigate the changes in collision cross section that occur as a result of complexation, providing additional evidence for this binding mode. Finally, nuclear magnetic resonance spectroscopy was used to track chemical shift changes upon binding. The results obtained confirm that these complexes adopt canonical collapsed structures and demonstrate the strength of the interaction between the peptides and CaM. An understanding of these molecular recognition events provides insights into the underlying mechanism of the amphibian host-defense system.
Keywords: Calmodulin; Oligopeptides; Amphibian Proteins; Nuclear Magnetic Resonance, Biomolecular; Signal Transduction; Protein Binding; Amino Acid Sequence; Nitric Oxide Synthase Type I; Molecular Sequence Data; Nitric Oxide; Models, Molecular; Antimicrobial Cationic Peptides
Rights: © 2014 American Chemical Society
RMID: 0030017124
DOI: 10.1021/bi5004124
Appears in Collections:IPAS publications

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