CPR-C4 is a highly conserved novel protease from the Candidate Phyla Radiation with remote structural homology to human vasohibins.

CPR-C4 is a highly conserved novel protease from the Candidate Phyla Radiation with remote structural homology to human vasohibins.
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DOI:
10.1016/j.jbc.2022.101919
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发表时间:
2022-05
影响因子:
4.8
通讯作者:
Pohl, Ehmke
Pohl, Ehmke
中科院分区:
生物学2区
文献类型:
--
作者:
Cornish, Katy A. S.;Lange, Joanna;Aevarsson, Arnthor;Pohl, Ehmke

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候选门辐射是最近发现的细菌生命领域的巨大扩展,由基本上没有特征的门组成,缺乏孤立的代表。这一未开发的遗传多样性领域提供了丰富的新蛋白质,在生命科学领域具有潜在的应用。在这里,我们介绍了CPR-C4的结构和功能阐明,CPR-C4是一种来自嗜热候选Phyla辐射生物基因组的假设蛋白质,通过宏基因组测序鉴定。我们的分析表明,CPR-C4是一个高度保守的蛋白质家族内的候选门辐射的成员。CPR-C4作为半胱氨酸蛋白酶的功能是通过与智人vasohibins的远程结构相似性预测的,随后用基于荧光的活性测定进行实验证实。此外,详细的结构和序列比对分析,使非典型的半胱氨酸-组氨酸-亮氨酸(羰基)催化三联体的鉴定。CPR-C4和人血管收缩素之间意想不到的结构和功能相似性表明,仅在序列水平上无法检测到进化关系。
The Candidate Phyla Radiation is a recently uncovered and vast expansion of the bacterial domain of life, made up of largely uncharacterized phyla that lack isolated representatives. This unexplored territory of genetic diversity presents an abundance of novel proteins with potential applications in the life-science sectors. Here, we present the structural and functional elucidation of CPR-C4, a hypothetical protein from the genome of a thermophilic Candidate Phyla Radiation organism, identified through metagenomic sequencing. Our analyses revealed that CPR-C4 is a member of a family of highly conserved proteins within the Candidate Phyla Radiation. The function of CPR-C4 as a cysteine protease was predicted through remote structural similarity to the Homo sapiens vasohibins and subsequently confirmed experimentally with fluorescence-based activity assays. Furthermore, detailed structural and sequence alignment analysis enabled identification of a noncanonical cysteine-histidine-leucine(carbonyl) catalytic triad. The unexpected structural and functional similarities between CPR-C4 and the human vasohibins suggest an evolutionary relationship undetectable at the sequence level alone.
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