Structure-function analysis of the histidine permease and comparison with cystic fibrosis mutations.
Structure-function analysis of the histidine permease and comparison with cystic fibrosis mutations.
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DOI：
10.1016/s0021-9258(18)55121-8
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发表时间：
1991-10
期刊：
影响因子：
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通讯作者：
V. Shyamala;V. Baichwal;E. Beall;G. Ames
中科院分区：
文献类型：
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作者：
V. Shyamala;V. Baichwal;E. Beall;G. Ames
交通ATP酶构成转运蛋白的超家族，其包括原核通透酶和医学上重要的真核蛋白，如多药耐药P-糖蛋白和囊性纤维化基因产物。我们提出了一个结构-功能分析这个超家族的成员，原核组氨酸通透酶，使用在体外和体内产生的突变，并测定几个生化功能。该分析支持先前预测的结构模型，并允许将特定功能分配给几个预测的结构特征。形成核苷酸结合口袋的二级结构特征的突变通常导致ATP结合活性的丧失。螺旋结构域中的突变保留ATP结合活性。已经鉴定了几种突变，其可能影响ATP水解和膜易位之间的信号传导机制。我们将我们的发现与最近对囊性纤维化突变的生化和遗传分析相关联。
Traffic ATPases constitute a superfamily of transporters that include prokaryotic permeases and medically important eukaryotic proteins, such as the multidrug resistance P-glycoprotein and the cystic fibrosis gene product. We present a structure-function analysis of a member of this superfamily, the prokaryotic histidine permease, using mutations generated both in vitro and in vivo, and assaying several biochemical functions. The analysis supports a previously predicted structural model and allows the assignment of specific functions to several predicted structural features. Mutations in the secondary structure features which form the nucleotide-binding pocket in general cause the loss of ATP binding activity. Mutations in the helical domain retain ATP binding activity. Several mutations have been identified which may affect the signaling mechanism between ATP hydrolysis and membrane translocation. We relate our findings to those emerging from the recent biochemical and genetic analyses of cystic fibrosis mutations.