期刊
JOURNAL OF INORGANIC BIOCHEMISTRY
卷 188, 期 -, 页码 62-75出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2018.08.010
关键词
Small heat shock protein; Mycobacterium leprae HSP18; Molecular chaperone; Spectroscopy; Metal ions; Protein-metal ion interaction
资金
- UGC, New Delhi, India
- IIT Bhubaneswar
- ICMR, India [45/25/2012-Bio/BMS]
Mycobacterium leprae uptakes various bivalent metal ions via different transporters in host species. Uptake of Cu2+ and Zn2+ are essential for generation of superoxide dismutases and catalases, which provide defense against reactive oxygen species mediated death of this pathogen in macrophages. Furthermore, it has also been noticed that levels of different bivalent metal ions (Ca2+, Mg2+, Cu2+ and Zn2+) in blood serum are altered in leprotic patients. Mycobacterium leprae HSP18 is an immunodominant antigen which helps in growth and survival of Mycobacterium leprae in host species. A possible link can exist between HSP18 and aberration of bivalent metal ion homeostasis. Therefore, we investigated the interaction of these four bivalent metal ions with HSP18 and found that the protein only interacts with Zn2+ and Cu2+. Such association process is reversible and moderately high affinity in nature with unit binding stoichiometry. Theoretical studies revealed that the most probable site for Zn2+-binding lies in the N-terminal domain; While, the same for Cu2+-binding lies in the alpha-crystallin domain of HSP18. Binding of Zn2+/Cu2+ to IISP18 brings about subtle changes in the secondary and tertiary structure of HSP18 but are distinctly opposite in nature. While Zn2+ causes oligomeric association, Cu2+ leads to oligomeric dissociation of HSP18. Structural stability, surface hydrophobicity and chaperone activity of HSP18 are enhanced on Zn2+ binding, while all of them are reduced upon Cu2+ binding. Altogether, metal ions binding to HSP18 regulate its function which may have far reaching effect on the survival and pathogenicity of Mycobacterium leprae in host species.
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