Kaushik Vineeta, Goel Manisha
Department of Biophysics, University of Delhi South Campus, New Delhi, India.
Front Microbiol. 2021 Oct 7;12:751049. doi: 10.3389/fmicb.2021.751049. eCollection 2021.
Cis-trans isomerization of the peptide bond prior to proline is an intrinsically slow process but plays an essential role in protein folding. isomerization reaction is catalyzed by Peptidyl-prolyl isomerase (PPIases), a category of proteins widely distributed among all the three domains of life. The present study is majorly focused on the distribution of different types of PPIases in the archaeal domain. All the three hitherto known families of PPIases (namely FKBP, Cyclophilin and parvulin) were studied to identify the evolutionary conservation across the phylum archaea. The basic function of cyclophilin, FKBP and parvulin has been conserved whereas the sequence alignment suggested variations in each clade. The conserved residues within the predicted motif of each family are unique. The available protein structures of different PPIase across various domains were aligned to ascertain the structural variation in the catalytic site. The structural alignment of native PPIase proteins among various groups suggested that the apo-protein may have variable conformations but when bound to their specific inhibitors, they attain similar active site configuration. This is the first study of its kind which explores the distribution of archaeal PPIases, along with detailed structural and functional analysis of each type of PPIase found in archaea.
脯氨酸之前的肽键顺反异构化是一个内在的缓慢过程，但在蛋白质折叠中起重要作用。异构化反应由肽基脯氨酰异构酶（PPIases）催化，这是一类广泛分布于生命所有三个域中的蛋白质。本研究主要关注不同类型的PPIases在古菌域中的分布。对迄今为止已知的所有三个PPIases家族（即FKBP、亲环蛋白和小菌素）进行了研究，以确定古菌门中的进化保守性。亲环蛋白、FKBP和小菌素的基本功能得到了保留，而序列比对表明每个进化枝存在差异。每个家族预测基序内的保守残基是独特的。对不同结构域的不同PPIase的可用蛋白质结构进行比对，以确定催化位点的结构变异。不同组之间天然PPIase蛋白的结构比对表明，脱辅基蛋白可能具有可变构象，但当与它们的特异性抑制剂结合时，它们会获得相似的活性位点构型。这是同类研究中的首次探索古菌PPIases的分布，并对古菌中发现的每种类型的PPIase进行详细的结构和功能分析。
