利用酵母模型对威尔逊病基因（ATP7B）新突变进行功能表征。

Functional characterization of new mutations in Wilson disease gene (ATP7B) using the yeast model.

作者信息

Papur Ozlenen Simsek, Terzioglu Orhan, Koc Ahmet

机构信息

Department of Medical Biology and Genetics, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey.

Department of Molecular Biology and Genetics, Izmir Institute of Technology, 35430 Urla, Izmir, Turkey.

出版信息

J Trace Elem Med Biol. 2015;31:33-6. doi: 10.1016/j.jtemb.2015.02.006. Epub 2015 Mar 5.

DOI:10.1016/j.jtemb.2015.02.006

PMID:26004889

Abstract

The Wilson disease gene, a copper transporting ATPase (Atp7b), is responsible for the sequestration of Cu into secretory vesicles, and this function is exhibited by the orthologous Ccc2p in the yeast. In this study, we aimed to characterize clinically relevant new mutations of human ATP7B (p.T788I, p.V1036I and p.R1038G-fsX83) in yeast lacking the CCC2 gene. Expression of human wild type ATP7B gene in ccc2Δ mutant yeast restored the growth deficiency and copper transport activity; however, expression of the mutant forms did not restore the copper transport functions and only partially supported the cell growth. Our data support that p.T788I, p.V1036I and p.R1038G-fsX83 mutations cause functional deficiency in ATP7B functions and suggest that these residues are important for normal ATP7B function.

摘要

威尔逊病基因是一种铜转运ATP酶（Atp7b），负责将铜隔离到分泌小泡中，酵母中的直系同源物Ccc2p也具有此功能。在本研究中，我们旨在鉴定在缺乏CCC2基因的酵母中人类ATP7B的临床相关新突变（p.T788I、p.V1036I和p.R1038G-fsX83）。在ccc2Δ突变酵母中表达人类野生型ATP7B基因可恢复生长缺陷和铜转运活性；然而，突变形式的表达并未恢复铜转运功能，仅部分支持细胞生长。我们的数据支持p.T788I、p.V1036I和p.R1038G-fsX83突变导致ATP7B功能的功能缺陷，并表明这些残基对正常ATP7B功能很重要。