Haas Crysten E, Rodionov Dmitry A, Kropat Janette, Malasarn Davin, Merchant Sabeeha S, de Crécy-Lagard Valérie
Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA.
BMC Genomics. 2009 Oct 12;10:470. doi: 10.1186/1471-2164-10-470.
COG0523 proteins are, like the nickel chaperones of the UreG family, part of the G3E family of GTPases linking them to metallocenter biosynthesis. Even though the first COG0523-encoding gene, cobW, was identified almost 20 years ago, little is known concerning the function of other members belonging to this ubiquitous family.
Based on a combination of comparative genomics, literature and phylogenetic analyses and experimental validations, the COG0523 family can be separated into at least fifteen subgroups. The CobW subgroup involved in cobalamin synthesis represents only one small sub-fraction of the family. Another, larger subgroup, is suggested to play a predominant role in the response to zinc limitation based on the presence of the corresponding COG0523-encoding genes downstream from putative Zur binding sites in many bacterial genomes. Zur binding sites in these genomes are also associated with candidate zinc-independent paralogs of zinc-dependent enzymes. Finally, the potential role of COG0523 in zinc homeostasis is not limited to Bacteria. We have predicted a link between COG0523 and regulation by zinc in Archaea and show that two COG0523 genes are induced upon zinc depletion in a eukaryotic reference organism, Chlamydomonas reinhardtii.
This work lays the foundation for the pursuit by experimental methods of the specific role of COG0523 members in metal trafficking. Based on phylogeny and comparative genomics, both the metal specificity and the protein target(s) might vary from one COG0523 subgroup to another. Additionally, Zur-dependent expression of COG0523 and putative paralogs of zinc-dependent proteins may represent a mechanism for hierarchal zinc distribution and zinc sparing in the face of inadequate zinc nutrition.
COG0523蛋白与脲酶G家族的镍伴侣蛋白一样，是GTP酶G3E家族的一部分，将它们与金属中心生物合成联系起来。尽管第一个编码COG0523的基因cobW在近20年前就已被鉴定出来，但对于这个普遍存在的家族中其他成员的功能却知之甚少。
基于比较基因组学、文献和系统发育分析以及实验验证的综合方法，COG0523家族可至少分为15个亚组。参与钴胺素合成的CobW亚组仅占该家族的一小部分。另一个更大的亚组，基于许多细菌基因组中假定的Zur结合位点下游存在相应的编码COG0523的基因，被认为在对锌限制的反应中起主要作用。这些基因组中的Zur结合位点也与锌依赖性酶的候选锌非依赖性旁系同源物相关。最后，COG0523在锌稳态中的潜在作用并不局限于细菌。我们预测了古菌中COG0523与锌调控之间的联系，并表明在真核参考生物莱茵衣藻中，两个COG0523基因在锌耗尽时被诱导。
这项工作为通过实验方法探究COG0523成员在金属运输中的具体作用奠定了基础。基于系统发育和比较基因组学，金属特异性和蛋白质靶点可能因COG0523亚组的不同而有所差异。此外，COG0523的Zur依赖性表达以及锌依赖性蛋白的假定旁系同源物可能代表了在锌营养不足时进行分级锌分布和锌节约的一种机制。
