An atlas of the thioredoxin fold class reveals the complexity of function-enabling adaptations.
An atlas of the thioredoxin fold class reveals the complexity of function-enabling adaptations.
复制标题
DOI：
10.1371/journal.pcbi.1000541
复制
发表时间：
2009-10
影响因子：
4.3
通讯作者：
Babbitt PC
中科院分区：
文献类型：
--
作者：
Atkinson HJ;Babbitt PC
含有硫氧还蛋白 (Trx) 折叠的蛋白质组数量庞大且多样化。评估 Trx 折叠蛋白催化机制的变化对于了解其功能多样性和预测该类许多未表征成员的功能至关重要。 Trx 折叠类蛋白质保留了共同特征，包括二硫醇 CxxC 活性位点基序的变化，这些特征导致功能的传递。我们使用蛋白质相似性网络来指导分析结构和序列基序如何跟踪催化功能和分类类别，涵盖 Trx 折叠已知超家族的 4,082 个代表性序列。折叠类中的结构域结构多种多样且模块化，2.8% 的序列包含多个 Trx 折叠结构域。大多数成员蛋白质是细菌的。折叠类别表现出对 CxxC 活性位点基序的许多修饰 - 只有 56.8% 的蛋白质具有两个半胱氨酸，并且没有功能组对预期催化基序具有绝对保守性。仅一小部分 Trx 折叠序列得到了功能表征。这项工作提供了整个折叠类中结构域和催化机制的复杂分布的全局视图，表明每个超家族都包含 CxxC 活性位点的残余物。这项工作提供的统一背景可以指导不同 Trx 折叠超家族成员的比较，以深入了解它们的结构-功能关系，此处以硫氧还蛋白和过氧化还原蛋白为例。对于任何一大类蛋白质，已知的蛋白质序列远远多于实验所能检测到的序列。硫氧还蛋白折叠类就是这种情况，它是一个庞大而多样的蛋白质集合，其中一些已知可以催化新陈代谢的重要步骤。其他一些参与蛋白质折叠和外来化合物解毒等关键过程。许多未经研究的蛋白质可能参与其他重要的生物过程，并在医学和工业中具有有用的应用。我们使用一种新的基于网络的计算方法来创建硫氧还蛋白折叠类的基于相似性的图。这些图谱将未研究的蛋白质与类似的已充分表征的蛋白质并置，有助于显示现有知识在哪些方面可以帮助预测未表征序列的特性。该信息可用于识别这些序列中哪些是有趣的并且值得进行实验表征。我们还使用这些图来深入了解如何使用和修改共享的结构特征来影响不同亚类中的催化作用，从而更好地理解硫氧还蛋白折叠类中结构和功能之间的相互作用。
The group of proteins that contain a thioredoxin (Trx) fold is huge and diverse. Assessment of the variation in catalytic machinery of Trx fold proteins is essential in providing a foundation for understanding their functional diversity and predicting the function of the many uncharacterized members of the class. The proteins of the Trx fold class retain common features—including variations on a dithiol CxxC active site motif—that lead to delivery of function. We use protein similarity networks to guide an analysis of how structural and sequence motifs track with catalytic function and taxonomic categories for 4,082 representative sequences spanning the known superfamilies of the Trx fold. Domain structure in the fold class is varied and modular, with 2.8% of sequences containing more than one Trx fold domain. Most member proteins are bacterial. The fold class exhibits many modifications to the CxxC active site motif—only 56.8% of proteins have both cysteines, and no functional groupings have absolute conservation of the expected catalytic motif. Only a small fraction of Trx fold sequences have been functionally characterized. This work provides a global view of the complex distribution of domains and catalytic machinery throughout the fold class, showing that each superfamily contains remnants of the CxxC active site. The unifying context provided by this work can guide the comparison of members of different Trx fold superfamilies to gain insight about their structure-function relationships, illustrated here with the thioredoxins and peroxiredoxins. For any large class of proteins, far more protein sequences are known than can be examined experimentally. This is the case with the thioredoxin fold class, a large and diverse collection of proteins, some of which are known to catalyze important steps in metabolism. Some others participate in key processes like protein folding and detoxification of foreign compounds. Many of the unstudied proteins likely participate in other important biological processes and have useful applications in medicine and industry. We used a new network-based computational approach to create similarity-based maps of the thioredoxin fold class. These maps juxtapose unstudied proteins with similar well-characterized proteins, helping to show where existing knowledge can help predict properties of uncharacterized sequences. This information can be used to identify which of these sequences are interesting and deserve experimental characterization. We also used the maps to gain insight about how shared structural features are used and modified to affect catalysis in the different subclasses, leading to a better understanding of the interplay between structure and function in the thioredoxin fold class.
登录
查看更多内容
Pfam：氏族、网络工具和服务。
影响因子：
14.9
作者：
Finn, Robert D.;Mistry, Jaina;Schuster-Bockler, Benjamin;Griffiths-Jones, Sam;Hollich, Volker;Lassmann, Timo;Moxon, Simon;Marshall, Mhairi;Khanna, Ajay;Durbin, Richard;Eddy, Sean R.;Sonnhammer, Erik L. L.;Bateman, Alex
通讯作者：
Bateman, Alex
影响因子：
2.9
作者：
Copley, SD;Novak, WRP;Babbitt, PC
通讯作者：
Babbitt, PC
影响因子：
4.8
作者：
Alanen, Heli I.;Williamson, Richard A.;Ruddock, Lloyd W.
通讯作者：
Ruddock, Lloyd W.
影响因子：
4.8
作者：
Fernandes, AP;Fladvad, M;Vlamis-Gardikas, A
通讯作者：
Vlamis-Gardikas, A
DOI：
10.1073/pnas.0800019105
发表时间：
2008-05-13
影响因子：
11.1
作者：
Banci, Lucia;Bertini, Ivano;Palumaa, Peep
通讯作者：
Palumaa, Peep