2MP9

Solution structure of an potent antifungal peptide Cm-p5 derived from C. muricatus

Summary for 2MP9

• Entry DOI: 10.2210/pdb2mp9/pdb
• NMR Information: BMRB: 19973
• Descriptor: Antifungal peptide (1 entity in total)
• Functional Keywords: helical peptide, antimicrobial, antimicrobial protein
• Biological source: Cenchritis muricatus (Beaded periwinkle)
• Total number of polymer chains: 1
• Total formula weight: 1485.73

Authors

Sun, Z.J.,Heffron, G.,Mcbeth, C.,Wagner, G.,Otero-Gonzales, A.J.,Starnbach, M.N. (deposition date: 2014-05-14, release date: 2015-08-12, Last modification date: 2024-10-16)

Primary citation

Lopez-Abarrategui, C.,McBeth, C.,Mandal, S.M.,Sun, Z.J.,Heffron, G.,Alba-Menendez, A.,Migliolo, L.,Reyes-Acosta, O.,Garcia-Villarino, M.,Nolasco, D.O.,Falcao, R.,Cherobim, M.D.,Dias, S.C.,Brandt, W.,Wessjohann, L.,Starnbach, M.,Franco, O.L.,Otero-Gonzalez, A.J.
Cm-p5: an antifungal hydrophilic peptide derived from the coastal mollusk Cenchritis muricatus (Gastropoda: Littorinidae).
Faseb J., 29:3315-3325, 2015

PubMed Abstract: Antimicrobial peptides form part of the first line of defense against pathogens for many organisms. Current treatments for fungal infections are limited by drug toxicity and pathogen resistance. Cm-p5 (SRSELIVHQRLF), a peptide derived from the marine mollusk Cenchritis muricatus peptide Cm-p1, has a significantly increased fungistatic activity against pathogenic Candida albicans (minimal inhibitory concentration, 10 µg/ml; EC50, 1.146 µg/ml) while exhibiting low toxic effects against a cultured mammalian cell line. Cm-p5 as characterized by circular dichroism and nuclear magnetic resonance revealed an α-helical structure in membrane-mimetic conditions and a tendency to random coil folding in aqueous solutions. Additional studies modeling Cm-p5 binding to a phosphatidylserine bilayer in silico and isothermal titration calorimetry using lipid monophases demonstrated that Cm-p5 has a high affinity for the phospholipids of fungal membranes (phosphatidylserine and phosphatidylethanolamine), only moderate interactions with a mammalian membrane phospholipid, low interaction with ergosterol, and no interaction with chitin. Adhesion of Cm-p5 to living C. albicans cells was confirmed by fluorescence microscopy with FITC-labeled peptide. In a systemic candidiasis model in mice, intraperitoneal administration of Cm-p5 was unable to control the fungal kidney burden, although its low amphiphaticity could be modified to generate new derivatives with improved fungicidal activity and stability.

PubMed: 25921828
DOI: 10.1096/fj.14-269860

Experimental method

SOLUTION NMR