DIMERIZATION OF HUMAN GROWTH-HORMONE BY ZINC

DIMERIZATION OF HUMAN GROWTH-HORMONE BY ZINC
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DOI:
10.1126/science.1907025
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发表时间:
1991-08-02
期刊:
影响因子:
56.9
通讯作者:
WELLS, JA
WELLS, JA
中科院分区:
综合性期刊1区
文献类型:
--
作者:
CUNNINGHAM, BC;MULKERRIN, MG;WELLS, JA

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分子排阻色谱和沉降平衡研究表明,锌离子(Zn 2+)可诱导人生长激素(hGH)的二聚化。Zn-65(2+)与hGH结合的Scatchard分析表明,hGH的每个二聚体中有两个Zn+离子以协同方式缔合。钴(II)可以取代激素二聚体中的Zn 2+,并给出了由含氧和含氮配体以四面体方式配位的钴的可见光谱特征。用丙氨酸取代hGH中潜在的Zn 2+配体(His 18、His 21和Glu 174),可减弱Zn 2+结合和hGH二聚体形成。Zn+-hGH二聚体在盐酸胍中变性时比单体hGH更稳定。形成的Zn 2 +-hGH二聚体复合物可能是重要的hGH在分泌颗粒中的存储。
Size-exclusion chromatography and sedimentation equilibrium studies demonstrated that zinc ion (Zn 2+) induced the dimerization of human growth hormone (hGH). Scatchard analysis of Zn-65(2+) binding to hGH showed that two Zn+ ions associate per dimer of hGH in a cooperative fashion. Cobalt (II) can substitute for Zn2+ in the hormone dimer and gives a visible spectrum characteristic of cobalt coordinated in a tetrahedral fashion by oxygen- and nitrogen-containing ligands. Replacement of potential Zn2+ ligands (His 18, His 21, and Glu 174) in hGH with alanine weakened both Zn2+ binding and hGH dimer formation. The Zn+-hGH dimer was more stable than monomeric hGH to denaturation in guanidine-HCl. Formation of a Zn2+-hGH dimeric complex may be important for storage of hGH in secretory granules.