Please use this identifier to cite or link to this item: http://cmuir.cmu.ac.th/jspui/handle/6653943832/54835
Title: Functional importance of the Gly cluster in transmembrane helix 2 of the Bordetella pertussis CyaA-hemolysin: Implications for toxin oligomerization and pore formation
Authors: Sirikran Juntapremjit
Niramon Thamwiriyasati
Chattip Kurehong
Panchika Prangkio
Lalida Shank
Busaba Powthongchin
Chanan Angsuthanasombat
Keywords: Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Nov-2015
Abstract: © 2015 Published by Elsevier Ltd. Adenylate cyclase-hemolysin (CyaA) is a major virulence factor of Bordetella pertussis causing whooping cough in humans. We previously showed that two transmembrane helices (α2 and α3) in the hemolysin domain (CyaA-Hly) are crucially involved in hemolytic activity. Here, PCR-based substitutions were employed to investigate a potential involvement in hemolysis of a series of four Gly residues (Gly530, Gly533, Gly537and Gly544) which map onto one face of a helical wheel plot of pore-lining helix 2. All CyaA-Hly mutant toxins were over-expressed in Escherichia coli as 126-kDa soluble proteins at levels comparable to the wild-type toxin. A drastic reduction in hemolytic activity against sheep erythrocytes was observed for three CyaA-Hly mutants, i.e. G530A, G533A and G537A, but not G544A, suggesting a functional importance of the Gly530-Gly533-Gly537cluster. A homology-based structure of the α2-loop-α3 hairpin revealed that this crucial Gly cluster arranged as a GXXGXXXG motif is conceivably involved in helix-helix association. Furthermore, a plausible pore model comprising three α2-loop-α3 hairpins implicated that Gly530XXGly533XXXGly537could function as an important framework for toxin oligomerization. Altogether, our present data signify for the first time that the Gly530-Gly533-Gly537cluster in transmembrane helix 2 serves as a crucial constituent of the CyaA-Hly trimeric pore structure.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84941985118&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/54835
ISSN: 18793150
00410101
Appears in Collections:CMUL: Journal Articles

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