Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland.
J Inorg Biochem. 2011 Sep;105(9):1220-5. doi: 10.1016/j.jinorgbio.2011.06.002. Epub 2011 Jun 17.
Histatins are a family of human salivary antimicrobial peptides. Histatin-5 (Hst-5, DSHAKRHHGYKRKFHEKHHSHRGY), a prominent member of this family contains an albumin-like, N-terminal Asp-Ser-His sequence, known to bind a Ni(II) ion in a square-planar geometry. Nickel is a strong allergen, and oral exposure to Ni(II) ions can elicit allergic reaction in sensitized persons. In contrast, prior oral exposure to nickel in non-sensitized persons can prevent sensitization. The fate of Ni(II) ions in saliva is obviously important for these processes, yet little is known about it. Using potentiometry, UV-visible titrations and circular dichroism, we determined stability constants for Ni(II) complexes of Hst-5 and two truncated analogs, 5Hst-5 (DSHAK) and 10Hst-5 (DSHAKRHHGY). The conditional binding constant at pH 7.4 for Hst-5 was 10(7.5±0.2), compared to the corresponding value for albumin, 10(6.8±0.3) (M. Sokołowska, A. Krężel, M. Dyba, Z. Szewczuk, W. Bal, Eur. J. Biochem. 269 (2002) 1323-1331). These values indicate that Hst-5 binds Ni(II) five times stronger than HSA. The simulated competition for Ni(II) between Hst-5 and albumin shows that significant amounts of Ni(II) ions may be carried by Hst-5 in vivo. Therefore, Hst-5 and other histatins should be considered as factors in nickel allergy and other forms of nickel toxicity.
组织胺是人类唾液中的一种抗微生物肽家族。组蛋白-5（Hst-5，DSHAKRHHGYKRKFHEKHHSHRGY）是该家族的重要成员，包含一个类似白蛋白的 N 端 Asp-Ser-His 序列，已知该序列可在正方形平面几何形状中结合 Ni(II) 离子。镍是一种很强的过敏原，口腔暴露于 Ni(II)离子会引起致敏个体的过敏反应。相比之下，先前在非致敏个体中口腔暴露于镍可以预防致敏。这些过程中 Ni(II)离子在唾液中的命运显然很重要，但对此知之甚少。我们使用电位法、紫外-可见滴定和圆二色性，确定了 Hst-5 及其两个截断类似物 5Hst-5（DSHAK）和 10Hst-5（DSHAKRHHGY）的 Ni(II) 配合物的稳定常数。在 pH 7.4 时，Hst-5 的条件结合常数为 10(7.5±0.2)，而白蛋白的相应值为 10(6.8±0.3)（M. Sokołowska、A. Krężel、M. Dyba、Z. Szewczuk、W. Bal，Eur. J. Biochem. 269 (2002) 1323-1331）。这些值表明 Hst-5 与 HSA 相比，结合 Ni(II) 的强度要强五倍。模拟 Hst-5 和白蛋白之间对 Ni(II)的竞争表明，体内可能有大量的 Ni(II)离子被 Hst-5 携带。因此，Hst-5 和其他组蛋白应该被视为镍过敏和其他形式的镍毒性的因素。
