Structural and mutational analyses of decarboxylated osteocalcin provide insight into its adiponectin‐inducing activity

Structural and mutational analyses of decarboxylated osteocalcin provide insight into its adiponectin‐inducing activity
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脱羧骨钙素的结构和突变分析有助于深入了解其脂联素诱导活性

DOI:
10.1002/1873-3468.14618
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发表时间:
2023
期刊:
影响因子:
3.5
通讯作者:
Kawano Keiichi
Kawano Keiichi
中科院分区:
生物学3区
文献类型:
--
作者:
Mizuguchi Mineyuki;Yokoyama Takeshi;Otani Takahito;Kuribara Shiori;Nabeshima Yuko;Obita Takayuki;Hirata Masato;Kawano Keiichi

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骨中的酸性环境对于骨代谢和脱羧骨钙素的产生是必需的,脱羧骨钙素作为葡萄糖代谢的调节激素起作用。在这里,我们描述了在酸性条件下脱羧骨钙素的高分辨率X射线晶体结构。脱羧骨钙蛋白在pH 2.0时保留了天然骨钙蛋白的α-螺旋结构,在中性pH下具有三个γ-羧基谷氨酸残基。这意味着脱羧骨钙蛋白在骨中的酸性环境下是稳定的。此外,定点突变显示Glu 17和Glu 21对脱羧骨钙素的脂联素诱导活性很重要。这些发现表明脱羧骨钙素受体对骨钙素螺旋1上的负电荷有反应。
An acidic environment in bone is essential for bone metabolism and the production of decarboxylated osteocalcin, which functions as a regulatory hormone of glucose metabolism. Here, we describe the high‐resolution X‐ray crystal structure of decarboxylated osteocalcin under acidic conditions. Decarboxylated osteocalcin at pH 2.0 retains the α‐helix structure of native osteocalcin with three γ‐carboxyglutamic acid residues at neutral pH. This implies that decarboxylated osteocalcin is stable under an acidic environment in bone. In addition, site‐directed mutagenesis revealed that Glu17 and Glu21 are important for the adiponectin‐inducing activity of decarboxylated osteocalcin. These findings suggest that the receptor of decarboxylated osteocalcin responds to the negative charge in helix 1 of osteocalcin.
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发表时间: 2014-06
期刊: Frontiers in bioscience
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