Functional implications from crystal structures of the conserved Bacillus subtilis protein Maf with and without dUTP
Functional implications from crystal structures of the conserved Bacillus subtilis protein Maf with and without dUTP
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DOI：
10.1073/pnas.97.12.6328
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发表时间：
2000-06-06
影响因子：
11.1
通讯作者：
Egli, M
中科院分区：
文献类型：
--
作者：
Minasov, G;Teplova, M;Egli, M
功能未确定的蛋白质的三维结构可能会提供对其功能的洞察。当相应的基因在进化过程中被保守时，关于这类蛋白质的三维结构信息的潜在好处尤其明显，这意味着一个重要的功能，并且无法从它们的序列中推断出功能分类。枯草芽孢杆菌Maf蛋白是一个蛋白质家族的代表，该家族在古生物、原核生物和真核生物的许多完全测序的基因组中都有同源基因，但其功能尚不清楚。作为探索功能的辅助，我们以1.85埃的分辨率测定了该蛋白质的晶体结构。该结构与多个序列比对相结合，揭示了一个假定的活性部位。该位点存在磷酸离子，MAF的一部分与几种tRNA合成酶的反密码子结合域的结构相似，提示MAF可能是一种核酸结合蛋白。MAF-核苷三磷酸复合体的晶体结构支持这一假说，并暗示MAF的配体或底物为具有5‘-或3’-端磷酸基团的双或寡核苷酸。进一步的线索来自观察到MAF单体的结构与最近报道的詹纳什甲烷球菌Mj0226蛋白的结构相似。就像MAF一样，这个预测的NTPase的结构是作为结构基因组学试点项目的一部分确定的。从序列分析来看，Maf和Mj0226之间的结构关系不明显。这些结果强调了结构基因组学揭示以前被认为是无关的蛋白质家族之间新的意想不到的联系的潜力。
Three-dimensional structures of functionally uncharacterized proteins may furnish insight into their functions. The potential benefits of three-dimensional structural information regarding such proteins are particularly obvious when the corresponding genes are conserved during evolution, implying an important function, and no functional classification can be inferred from their sequences. The Bacillus subtilis Maf protein is representative of a family of proteins that has homologs in many of the completely sequenced genomes from archaea, prokaryotes, and eukaryotes, but whose function is unknown. As an aid in exploring function, we determined the crystal structure of this protein at a resolution of 1.85 Angstrom. The structure, in combination with multiple sequence alignment, reveals a putative active site. Phosphate ions present at this site and structural similarities between a portion of Maf and the anticodon-binding domains of several tRNA synthetases suggest that Maf may be a nucleic acid-binding protein. The crystal structure of a Maf-nucleoside triphosphate complex provides support for this hypothesis and hints at di- or oligonucleotides with either 5'- or 3'-terminal phosphate groups as ligands or substrates of Maf, A further clue comes from the observation that the structure of the Maf monomer bears similarity to that of the recently reported Methanococcus jannaschii Mj0226 protein. Just as for Maf, the structure of this predicted NTPase was determined as part of a structural genomics pilot project. The structural relation between Maf and Mj0226 was not apparent from sequence analysis approaches. These results emphasize the potential of structural genomics to reveal new unexpected connections between protein families previously considered unrelated.