Metallochaperones and metal-transporting ATPases: A comparative analysis of sequences and structures
Metallochaperones and metal-transporting ATPases: A comparative analysis of sequences and structures
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DOI：
10.1101/gr.196802
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发表时间：
2002-02-01
期刊：
影响因子：
7
通讯作者：
O'Halloran, TV
中科院分区：
文献类型：
--
作者：
Arnesano, F;Banci, L;O'Halloran, TV
一类新的金属运输蛋白质的比较结构基因组分析可以提供深入了解反应性辅因子，如铜和锌的细胞内化学。从金属伴侣Atx 1和铜转运ATP酶Ccc 2的第一个可溶性结构域的序列开始，使用同源性标准和金属结合基序x ′-x”-C-x“′-x”"-C，对可用的基因组进行搜索。通过限制我们自己与任何发现的蛋白质的20%的同一性，确定了几种可溶性铜转运蛋白，以及膜结合ATP酶的可溶性结构域。使用高分辨率溶液结构作为模板计算结构模型，并使用统计和能量标准对模型进行验证。从结构-功能关系的角度对残基的保守性和取代性进行了解释和讨论。势能面已被分析的蛋白质-蛋白质相互作用。我们发现，金属分子伴侣和他们的生理伙伴ATP酶从几个系统发育王国认识到彼此，通过静电，氢键和疏水相互作用的相互作用，在一种方式，精确地定向的金属结合侧链之间的快速金属转移，否则紧密的结合位点。最后，其他假定的金属转运蛋白提到，具有低同源性和/或不同的金属结合的共识基序，似乎使用类似的结构识别和转移。这一分析突出了该领域的丰富性和复杂性。
A comparative structural genomic analysis of a new class of metal-trafficking proteins can provide insights into the intracellular chemistry of reactive cofactors such as copper and zinc. Starting from the sequences of the metallochaperone Atx1 and from the first soluble domain of the copper-transporting ATPase Ccc2, both from yeast, a search on the available genomes was performed using a homology criterion and a metal-binding motif x'-x"-C-x"'-x""-C. By limiting ourselves to 20% identity with any of the proteins found, several soluble copper-transport proteins were identified, as well as soluble domains of membrane-bound ATPases. Structural models were calculated using high-resolution solution structures as templates, and the models were validated using statistical and energy criteria. Residue conservation and substitution have been interpreted and discussed in terms of structure-function relationship. The potential energy surfaces have been analyzed in terms of protein-protein interactions. We find that metallochaperones and their physiological partner ATPases from several phylogenetic kingdoms recognize one another, via an interplay of electrostatics, hydrogen bonding, and hydrophobic interactions, in a manner that precisely orients the metal-binding side chains for rapid metal transfer between otherwise tight binding sites. Finally, other putative metal-transport proteins are mentioned that have low homology and/or a different metal-binding consensus motif and that appear to use similar structures for recognition and transfer. This analysis highlights the wealth and the complexity of the field.