Recent progress of copper and nickel chaperones

Abstract

Maturation of copper-and nickel-containing enzymes relies on a battery of metallochaperones,which play an important role in the transport and trafficking of Cu or Ni,and assist the assembly of metallocenter in metalloenzymes.Significant progress on the structure and function of metallochaperones has been made in the past years,improving our understanding on the homeostasis of Cu/Ni in cells.Recent progress of Cu/Ni chaperones is summarized in this review.The blueprint of Cu import and homeostasis is briefly discussed followed by the structural and functional aspects of selected Cu chaperones, i.e. Atox1, Cox17 and CCS. Moreover, the putative relationships between Cu chaperones and drugs are discussed. The second part focuses on the maturation of hydrogenase and urease, in which a series of Ni chaperones interacts with each other to achieve the homeostasis of nickel. Selected structural complexes and in vivo functional study of the chaperones are emphasized, the 'crosstalk crosstalk' between the two maturation pathways is presented.

含銅/鎳金屬酶的成熟需要一系列的銅/鎳金屬伴侶蛋白,這些銅/鎳金屬伴侶蛋白分別參與銅或者鎳的轉運,對維持細胞體內銅/鎳金屬平衡至關重要,同時金屬酶完成金屬催化活性中心的組裝也依賴于這類伴侶蛋白。近年來關于銅/鎳金屬蛋白的研究取得可喜的進展,這些研究為進一步認識體內銅/鎳平衡體系提供了重要依據。本文首先簡要地介紹銅的攝取和細胞內平衡體系,接著著重介紹三個重要的銅轉運蛋白Atox1、Cox17和CCS關于結構和功能的進展,以及這些銅轉運蛋白和藥物相互作用的機理。然后詳細介紹在氫化酶和脲酶成熟路徑中參與了鎳的攝取、調節、轉運和存儲,維持細胞內鎳金屬平衡的鎳伴侶蛋白,并介紹了脲酶、氫化酶這兩條成熟路徑之間的聯系。