The folding catalyst protein disulfide isomerase is constructed of active and inactive thioredoxin modules
The folding catalyst protein disulfide isomerase is constructed of active and inactive thioredoxin modules
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DOI：
10.1016/s0960-9822(06)00119-9
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发表时间：
1997-04-01
期刊：
影响因子：
9.2
通讯作者：
Creighton, TE
中科院分区：
文献类型：
--
作者：
Kemmink, J;Darby, NJ;Creighton, TE
背景资料：蛋白质二硫键异构酶（PDI）是内质网中的一种多功能蛋白质，在蛋白质折叠过程中催化二硫键的形成、断裂和重排。将该蛋白质分解成其各个结构域已经证实了a和a'结构域的存在，其与硫氧还蛋白同源，具有相关的结构和活性。a和a'结构域均含有-Cys-Gly-His-Cys-活性位点序列基序。分子的其余部分主要由两个另外的结构域组成，命名为B和b '，基于有限的序列相似性，认为它们是序列重复。B和B'结构域的功能是未知的，直到现在，没有结构域的结构是knowed.Results：异源核磁共振（NMR）方法已被用来确定的全球折叠的PDI B结构域。该蛋白质具有α/β折叠，二级结构元件的顺序为β 1-α 1-β 2-α 2-β 3-α 3-β 4-β-5-α 4。这些链都是平行排列的，除了β 4是反平行的。B结构域的二级结构元件的排列与PDI的a结构域和普遍存在的氧化还原蛋白硫氧还蛋白中发现的排列相同; B结构域的三维折叠拓扑结构也与这些蛋白非常相似。我们通过NMR测定PDI的B结构域的整体折叠揭示了，与a结构域一样，B结构域含有硫氧还蛋白基序，即使B结构域与硫氧还蛋白家族的任何成员没有显著的氨基酸序列相似性。这一观察结果，连同迹象表明，B'域采用了类似的倍，表明PDI由活性？和无活性硫氧还蛋白模块。这些模块可能在进化过程中已经适应，以提供具有完整酶活性谱的PDI。(C)当前生物有限公司
Background: Protein disulfide isomerase (PDI), a multifunctional protein of the endoplasmic reticulum, catalyzes the formation, breakage and rearrangement of disulfide bonds during protein folding. Dissection of this protein into its individual domains has confirmed the presence of the a and a' domains, which are homologous to thioredoxin, having related structures and activities. The a and a' domains both contain a -Cys-Gly-His-Cys- active-site sequence motif. The remainder of the molecule consists primarily of two further domains, designated b and b', which are thought to be sequence repeats on the basis of a limited sequence similarity. The functions of the b and b' domains are unknown and, until now, the structure of neither domain was known.Results: Heteronuclear nuclear magnetic resonance (NMR) methods have been used to determine the global fold of the PDI b domain. The protein has an alpha/beta fold with the order of the elements of secondary structure being beta 1-alpha 1-beta 2-alpha 2-beta 3-alpha 3-beta 4-beta-5-alpha 4. The strands are all in a parallel arrangement with respect to each other, except for beta 4 which is antiparallel. The arrangement of the secondary structure elements of the b domain is identical to that found in the a domain of PDI and in the ubiquitous redox protein thioredoxin; the three-dimensional folding topology of the b domain is also very similar to that of these proteins.Conclusions: Our determination of the global fold of the b domain of PDI by NMR reveals that, like the a domain, the b domain contains the thioredoxin motif, even though the b domain has no significant amino-acid sequence similarities to any members of the thioredoxin family. This observation, together with indications that the b' domain adopts a similar fold, suggests that PDI consists of active? and inactive thioredoxin modules. These modules may have been adapted during evolution to provide PDI with its complete spectrum of enzymatic activities. (C) Current Biology Ltd.