Role of aromatic amino acids in receptor binding activity and subunit assembly of the cytolethal distending toxin of Aggregatibacter actinomycetemcomitans.

Infection and Immunity
Linsen CaoJoseph M DiRienzo

Abstract

The periodontal pathogen Aggregatibacter actinomycetemcomitans produces a cytolethal distending toxin (Cdt) that inhibits the proliferation of oral epithelial cells. Structural models suggest that the CdtA and CdtC subunits of the Cdt heterotrimer form two putative lectin domains with a central groove. A region of CdtA rich in heterocyclic amino acids (aromatic patch) appears to play an important role in receptor recognition. In this study site-specific mutagenesis was used to assess the contributions of aromatic amino acids (tyrosine and phenylalanine) to receptor binding and CdtA-CdtC assembly. Predominant surface-exposed aromatic residues that are adjacent to the aromatic patch region in CdtA or are near the groove located at the junction of CdtA and CdtC were studied. Separately replacing residues Y105, Y140, Y188, and Y189 with alanine in CdtA resulted in differential effects on binding related to residue position within the aromatic region. The data indicate that an extensive receptor binding domain extends from the groove across the entire face of CdtA that is oriented 180 degrees from the CdtB subunit. Replacement of residue Y105 in CdtA and residues Y61 and F141 in CdtC, which are located in or at the periphery of the ...Continue Reading

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Citations

Apr 8, 2011·Journal of Dental Research·M Damek-PoprawaJ M DiRienzo
Apr 9, 2014·Cells·Georgios N Belibasakis, Nagihan Bostanci
Jan 12, 2013·The Journal of Biological Chemistry·Amandeep GargiSteven R Blanke
Apr 21, 2010·Periodontology 2000·Jørgen Slots
Oct 17, 2009·Oral Microbiology and Immunology·D KawamotoM P A Mayer
Dec 18, 2008·FEMS Microbiology Letters·Joseph M DiRienzoJonathan Korostoff
Aug 26, 2016·Frontiers in Cellular and Infection Microbiology·Kathleen Boesze-BattagliaBruce J Shenker
Dec 19, 2019·Periodontology 2000·Casey ChenJørgen Slots

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