Schistocins: Novel antimicrobial peptides encrypted in the Schistosoma mansoni Kunitz Inhibitor SmKI-1,Biochimica et Biophysica Acta (BBA) - General Subjects

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Schistocins: Novel antimicrobial peptides encrypted in the Schistosoma mansoni Kunitz Inhibitor SmKI-1
Biochimica et Biophysica Acta (BBA) - General Subjects ( IF 2.8 ) Pub Date : 2021-08-10 , DOI: 10.1016/j.bbagen.2021.129989
B P O Santos ₁ , E S F Alves ₂ , C S Ferreira ₃ , A Ferreira-Silva ₄ , A Góes-Neto ₅ , R M Verly ₃ , L M Lião ₂ , S C Oliveira ₆ , M T Q de Magalhães ₁

Affiliation

Laboratório de Biofísica de Macromoléculas, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil; Programa Interunidades de Pós-graduação em Bioinformática, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil.
Laboratório de Ressonância Magnética Nuclear, Instituto de Química, Universidade Federal de Goiás, Goiânia, Goiás 74690-900, Brazil.
Laboratório de Síntese e Estrutura de Biomoléculas, Departamento de Química, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Diamantina, Minas Gerais 39100-000, Brazil.
Laboratório de Biologia Molecular e Computacional de Fungos, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil.
Programa Interunidades de Pós-graduação em Bioinformática, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil; Laboratório de Biologia Molecular e Computacional de Fungos, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil.
Programa Interunidades de Pós-graduação em Bioinformática, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil; Laboratório de Imunologia de Doenças Infecciosas, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil; Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), Conselho Nacional de Desenvolvimento Científico e Tecnológico, Ministério da Ciência Tecnologia e Inovação Salvador, Bahia, Brazil.

Background

Here we describe a new class of cryptides (peptides encrypted within a larger protein) with antimicrobial properties, named schistocins, derived from SmKI-1, a key protein in Shistosoma mansoni survival. This is a multi-functional protein with biotechnological potential usage as a therapeutic molecule in inflammatory diseases and to control schistosomiasis.

Methods

We used our algorithm enCrypted, to perform an in silico proteolysis of SmKI-1 and a screening for potential antimicrobial activity. The selected peptides were chemically synthesized, tested in vitro and evaluated by both structural (CD, NMR) and biophysical (ITC) studies to access their structure-function relationship.

Results

EnCrypted was capable of predicting AMPs in SmKI-1. Our biophysical analyses described a membrane-induced conformational change from random coil-to-α-helix and a peptide-membrane equilibrium for all schistocins. Our structural data allowed us to suggest a well-known mode of peptide-membrane interaction in which electrostatic attraction between the cationic peptides and anionic membranes results in the bilayer disordering. Moreover, the NMR H/D exchange data with the higher entropic contribution observed for the peptide-membrane interaction showed that schistocins have different orientations upon the membrane.

Conclusions

This work demonstrate the robustness for using the physicochemical features of predicted peptides in the identification of new bioactive cryptides. Besides, it demonstrates the relevance of combining these analyses with biophysical methods to understand the peptide-membrane affinity and improve further algorithms.

General significance

Bioprospecting cryptides can be conducted through data mining of protein databases demonstrating the success of our strategy. The peptides-based agents derived from SmKI-1 might have high impact for system-biology and biotechnology.

中文翻译：

Schistocins：在曼氏血吸虫 Kunitz 抑制剂 SmKI-1 中加密的新型抗菌肽

背景

在这里，我们描述了一类具有抗菌特性的新型隐肽（在更大的蛋白质中加密的肽），称为血吸虫素，源自 SmKI-1，这是曼氏血吸虫存活的关键蛋白质。这是一种多功能蛋白质，具有生物技术潜力，可用作炎症疾病的治疗分子和控制血吸虫病。

方法

我们使用我们的算法 enCrypted，对SmKI-1进行计算机模拟蛋白水解并筛选潜在的抗菌活性。选定的肽经过化学合成、体外测试并通过结构（CD、NMR）和生物物理（ITC）研究进行评估，以了解它们的结构-功能关系。

结果

EnCrypted 能够预测 SmKI-1 中的 AMP。我们的生物物理分析描述了所有血吸虫素从无规卷曲到α-螺旋的膜诱导构象变化和肽膜平衡。我们的结构数据使我们能够提出一种众所周知的肽 - 膜相互作用模式，其中阳离子肽和阴离子膜之间的静电吸引力导致双层无序。此外，对于肽-膜相互作用观察到的具有较高熵贡献的 NMR H/D 交换数据表明，血吸虫素在膜上具有不同的方向。