Thiol-disulfide exchange in an immunoglobulin-like fold: Structure of the N-terminal domain of DsbD
Thiol-disulfide exchange in an immunoglobulin-like fold: Structure of the N-terminal domain of DsbD
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DOI：
10.1021/bi016038l
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发表时间：
2002-06-04
期刊：
影响因子：
2.9
通讯作者：
Missiakas, D
中科院分区：
文献类型：
--
作者：
Goulding, CW;Sawaya, MR;Missiakas, D
大肠杆菌DsbD通过质膜运输电子，这是导致蛋白质二硫键减少的一种途径。三个分泌的硫氧还蛋白样因子DsbC、DsbE和DsbG通过氧化活性中心C-X-X-C基序来减少蛋白质的二硫键，从而产生二硫键。DsbD催化DsbC、DsbE和DsbG的二硫键还原，但不催化硫氧还蛋白类氧化剂DsbA的还原。DsbC、DsbE和DsbG的还原是通过将电子从细胞质的硫氧还蛋白转移到DsbD的C末端硫氧还蛋白样结构域(DsbD(C))来实现的。DsbD的N-末端结构域，DsbD(N)，在电子传递中充当一个通用的适配器，并且能够与氧化的DsbC、DsbE或DsbG以及与还原的DsbD(C)形成g二硫化物。分离的DsbD(N)在体外具有电子传递功能。结晶的DsbD(N)呈免疫球蛋白样折叠，包含两个活性部位半胱氨酸，C-103和C-109，在β-链之间形成二硫键。DsbD(N)的二硫键不受环境影响，并由苯丙氨酸(F-70)封端。讨论了DsbD(N)的免疫球蛋白折叠可能提供与硫氧还蛋白样因子的区别相互作用，从而触发苯丙氨酸帽移动随后的二硫键再排列的模型。
Escherichia coli DsbD transports electrons across the plasma membrane, a pathway that leads to the reduction of protein disulfide bonds. Three secreted thioredoxin-like factors, DsbC, DsbE, and DsbG, reduce protein disulfide bonds whereby an active site C-X-X-C motif is oxidized to generate a disulfide bond. DsbD catalyzes the reduction of the disulfide of DsbC, DsbE, and DsbG but not of the thioredoxin-like oxidant DsbA. The reduction of DsbC, DsbE, and DsbG occurs by transport of electrons from cytoplasmic thioredoxin to the C-terminal thioredoxin-like domain of DsbD (DsbD(C)). The N-terminal domain of DsbD, DsbD(N), acts as a versatile adaptor in electron transport and is capable of forming g disulfides with oxidized DsbC, DsbE, or DsbG as well as with reduced DsbD(C). Isolated DsbD(N) is functional in electron transport in vitro. Crystallized DsbD(N) assumes an immunoglobulin-like fold that encompasses two active site cysteines, C-103 and C-109, forming a disulfide bond between beta-strands. The disulfide of DsbD(N) is shielded from the environment and capped by a phenylalanine (F-70). A model is discussed whereby the immunoglobulin fold of DsbD(N) may provide for the discriminating interaction with thioredoxin- like factors, thereby triggering movement of the phenylalanine cap followed by disulfide rearranaement.