Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/122680
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Type: Journal article
Title: The structure and metal binding properties of Chlamydia trachomatis YtgA
Author: Luo, Z.
Neville, S.L.
Campbell, R.
Morey, J.R.
Menon, S.
Thomas, M.
Eijkelkamp, B.A.
Ween, M.P.
Huston, W.M.
Kobe, B.
McDevitt, C.A.
Citation: Journal of Bacteriology, 2020; 202(1):e00580-19-1-e00580-19-17
Publisher: American Society for Microbiology
Issue Date: 2020
ISSN: 0021-9193
1098-5530
Statement of
Responsibility: 
Zhenyao Luo, Stephanie L. Neville, Rebecca Campbell, Jacqueline R. Morey, Shruti Menon, Mark Thomas, Bart A. Eijkelkamp, Miranda P. Ween, Wilhelmina M. Huston, Bostjan Kobe, Christopher A. McDevitt
Abstract: The obligate intracellular pathogen Chlamydia (C.) trachomatis is a globally significant cause of sexually transmitted bacterial infections and the leading etiological agent of preventable blindness. The first-row transition metal iron (Fe) plays critical roles in chlamydial cell biology and acquisition of this nutrient is essential for the survival and virulence of the pathogen. Nevertheless, how C. trachomatis acquires Fe from host cells is not well understood, as it lacks genes encoding known siderophore biosynthetic pathways, receptors for host Fe-storage proteins, and the Fe acquisition machinery common to many bacteria. Recent studies have suggested that C. trachomatis directly acquires host Fe via the ATP-binding cassette permease YtgABCD. Here, we characterized YtgA, the periplasmic solute binding protein component of the transport pathway, that has been implicated in scavenging Fe(III) ions. The structure of Fe(III)-bound YtgA was determined at 2.0 Å resolution with the bound ion coordinated via a novel geometry (N3O2). This unusual coordination suggested a highly plastic metal-binding site in YtgA capable of interacting with other cations. Biochemical analyses showed that the metal-binding site of YtgA was not restricted to interaction with only Fe(III) ions, but could bind all transition metal ions examined. However, only Mn(II), Fe(II) and Ni(II) ions bound reversibly to YtgA, with Fe being the most abundant cellular transition metal in C. trachomatis Collectively, these findings show that YtgA is the metal-recruiting component of the YtgABCD permease and is most likely involved in acquisition of Fe(II) and Mn(II) from host cells. Importance: Chlamydia trachomatis is the most common bacterial sexually transmitted infection in developed countries with an estimated global prevalence of 4.2% in the 15 to 49-year age group. Although infection is asymptomatic in more than 80% of infected women, about 10% of cases result in serious disease. Infection by C. trachomatis is dependent on the ability to acquire essential nutrients, such as the transition metal iron, from the host cells. In this study, we show that the iron is the most abundant transition metal in C. trachomatis and report the structural and biochemical properties of the iron-recruiting protein YtgA. Knowledge of the high-resolution structure of YtgA will provide a platform for future structure-based antimicrobial design approaches.
Keywords: YtgA; solute binding protein; Chlamydia trachomatis; iron acquisition; ABC transporter; heavy metals; iron; structural biology; substrate binding protein
Rights: © 2019 American Society for Microbiology. All Rights Reserved.
RMID: 1000002449
DOI: 10.1128/JB.00580-19
Grant ID: http://purl.org/au-research/grants/nhmrc/1071659
http://purl.org/au-research/grants/nhmrc/1122582
http://purl.org/au-research/grants/arc/DP170102102
http://purl.org/au-research/grants/nhmrc/1142695
http://purl.org/au-research/grants/nhmrc/1110971
http://purl.org/au-research/grants/arc/FL180100109
http://purl.org/au-research/grants/arc/FT170100006
Appears in Collections:Microbiology and Immunology publications

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