Rim domain loops of staphylococcal b-pore forming bi-component toxin S-components recognize target human erythrocytes in a coordinated manner

Zhao Peng, Miyu Takeshita, Nao Shibata, Hideaki Tada, Yoshikazu Tanaka, Jun Kaneko

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Staphylococcus aureus bi-component pore-forming toxins consist of S-And F-components, and form hetero-octameric beta-barrel pores on target blood cell membranes. Among them, c-haemolysin (Hlg2 and F-component of Luk (LukF)) and LukED (LukE and LukD) possess haemolytic activity, whereas the Panton-Valentine leukocidin (LukS-PV and LukFPV) does not lyse human erythrocytes. Here, we focussed on four loop structures in the rim domain of S-component, namely loops-1,-2,-3 and-4, and found that replacement of Loop-4 in both Hlg2 and LukE with that of LukS-PV abolished their haemolytic activity. Furthermore, LukS-PV gained haemolytic activity by Loop-4 exchange with Hlg2 or LukE, suggesting that Loop-4 of these S-components determined erythrocyte specificity. LOOP-1 and-2 enhanced the erythrocytes-binding ability of both components. Although Hlg2 and LukE recognize Duffy antigen receptor for chemokines on human erythrocytes, the ability of Loop-4 was not complementary between Hlg2 and LukE. Exchange of Hlg2 with LukE Loop-4 showed weaker activity than intact Hlg2, and LukE mutant with Hlg2 Loop-4 lost its haemolytic activity in combination of LukD. Interestingly, the haemolytic activities of these Loop-4 exchange mutants were affected by F-component, namely LukF enhanced haemolytic activities of these Hlg2 and LukE Loop-4 mutants, and also haemolytic activity of LukS-PV mutant with LukE Loop-4.

Original languageEnglish
Pages (from-to)93-102
Number of pages10
JournalJournal of biochemistry
Volume164
Issue number2
DOIs
Publication statusPublished - 2018 Jan 1

Keywords

  • Bacterial
  • CCR5.
  • Drugs
  • Protein
  • Protein-protein interactions
  • S-components
  • Staphylococcal bicomponent toxin
  • Toxins
  • Xenobiotics

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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