Metallocluster transactions: dynamic protein interactions guide the biosynthesis of Fe–S clusters in bacteria
Metallocluster transactions: dynamic protein interactions guide the biosynthesis of Fe–S clusters in bacteria
复制标题
金属簇交易：动态蛋白质相互作用指导细菌中 Fe–S 簇的生物合成
DOI：
10.1042/bst20180365
复制
发表时间：
2018
影响因子：
3.9
通讯作者：
Dos Santos, Patricia C.
中科院分区：
文献类型：
--
作者：
Zheng, Chenkang;Dos Santos, Patricia C.
铁-硫(Fe-S)团簇是广泛存在于生命各个领域的辅因子。这些无机辅因子催化的化学反应是多样的，它们的相关酶参与了许多细胞过程。尽管有报道称Fe-S簇插入蛋白质中具有广泛的结构，但所有Fe-S簇的生物合成都始于2Fe-2S和4Fe-4S簇的简单单元的组装。有几个系统与细菌中铁-S簇的形成有关，这些细菌具有不同的系统发育起源和生物合成和调节成分的数量。然而，所有系统都通过类似的生物合成机制构建Fe-S簇，包括三个主要步骤：(1)半胱氨酸脱硫酶激活硫，(2)支架蛋白组装簇，(3)引导Fe-S单元输送到最终受体或参与形成复杂金属簇的生物合成酶。细菌中铁-S簇生物形成的另一个统一特征是，这些系统受到蛋白质相互作用网络的严格调控。因此，生物合成成分之间的瞬时蛋白质复合体的形成允许活性硫和铁-S中间体的直接转移，以防止氧损伤和与非生理靶标的反应。最近的研究揭示了相互签名序列基序的重要性，它使特定的蛋白质-蛋白质相互作用，从而指导生理供体和受体之间的交易。这些发现为细菌用来调节活性中间体流动的策略提供了洞察力，并提供了蛋白质条形码来揭示参与铁-S新陈代谢的尚未确定的细胞成分。
Iron–sulfur (Fe–S) clusters are ubiquitous cofactors present in all domains of life. The chemistries catalyzed by these inorganic cofactors are diverse and their associated enzymes are involved in many cellular processes. Despite the wide range of structures reported for Fe–S clusters inserted into proteins, the biological synthesis of all Fe–S clusters starts with the assembly of simple units of 2Fe–2S and 4Fe–4S clusters. Several systems have been associated with the formation of Fe–S clusters in bacteria with varying phylogenetic origins and number of biosynthetic and regulatory components. All systems, however, construct Fe–S clusters through a similar biosynthetic scheme involving three main steps: (1) sulfur activation by a cysteine desulfurase, (2) cluster assembly by a scaffold protein, and (3) guided delivery of Fe–S units to either final acceptors or biosynthetic enzymes involved in the formation of complex metalloclusters. Another unifying feature on the biological formation of Fe–S clusters in bacteria is that these systems are tightly regulated by a network of protein interactions. Thus, the formation of transient protein complexes among biosynthetic components allows for the direct transfer of reactive sulfur and Fe–S intermediates preventing oxygen damage and reactions with non-physiological targets. Recent studies revealed the importance of reciprocal signature sequence motifs that enable specific protein–protein interactions and consequently guide the transactions between physiological donors and acceptors. Such findings provide insights into strategies used by bacteria to regulate the flow of reactive intermediates and provide protein barcodes to uncover yet-unidentified cellular components involved in Fe–S metabolism.