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 “α-crystallin domain” of HSP18. Binding of Zn²⁺/Cu²⁺ to HSP18 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.

麻风分枝杆菌通过宿主物种中的不同转运蛋白吸收各种二价金属离子。摄取Cu ²⁺和Zn ²⁺对于产生超氧化物歧化酶和过氧化氢酶是必不可少的，超氧化物歧化酶和过氧化氢酶可防御巨噬细胞中活性氧介导的这种病原体死亡的防御。此外，还注意到麻风病患者血清中不同的二价金属离子（Ca 2 ⁺，Mg 2 ⁺，Cu ²⁺和Zn ²⁺）的水平发生了变化。麻风分枝杆菌HSP18是一种免疫显性抗原，有助于麻风分枝杆菌的生长和存活在宿主物种中。HSP18与二价金属离子稳态平衡之间可能存在联系。因此，我们研究了这四个二价金属离子与HSP18的相互作用，发现该蛋白质仅与Zn ²⁺和Cu ²⁺相互作用。这样的缔合过程是可逆的，并且本质上具有单位结合化学计量的适度高亲和力。理论研究表明，最可能的Zn ²⁺结合位点位于N末端域。然而，Cu ²⁺结合的相同之处在于HSP18的“α-晶状体结构域”。Zn ²⁺ / Cu ^2+的结合HSP18的突变导致HSP18的二级和三级结构发生细微变化，但本质上却截然相反。Zn ²⁺引起寡聚缔合，而Cu ²⁺导致HSP18寡聚解离。HSP18的结构稳定性，表面疏水性和分子伴侣活性在Zn ²⁺结合时得到增强，而所有这些在Cu ²⁺结合时都降低。总之，与HSP18结合的金属离子调节其功能，这可能对麻风分枝杆菌在宿主物种中的存活和致病性具有深远的影响。