Laboratório de Leishmanioses, Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP: 486 - CEP: 31.270-901, Belo Horizonte, MG, Brazil.
Laboratório de Biologia Celular e Patógenos Intracelulares, Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP: 486 - CEP: 31.270-901, Belo Horizonte, MG, Brazil.
Exp Parasitol. 2021 Feb;221:108048. doi: 10.1016/j.exppara.2020.108048. Epub 2020 Dec 9.
Leishmaniasis is a disease caused by trypanosomatid protozoa of the genus Leishmania. In the Americas, the species Leishmania amazonensis is predominantly associated with American cutaneous leishmaniasis (ACL) while L. infantum is an agent of visceral leishmaniasis (VL). The genome sequences of Leishmania spp. have shown that each genome can contain about 8000 genes encoding proteins, more than half of which have an unknown function (''hypotheticals") at the time of publication. To understand the biology and genome of the organisms, it is important to discover the function of these "hypothetical" proteins; however, few studies have focused on their characterizations. Previously, LinJ.30.3360 (a protein with unknown function) was identified as immunogenic to canine serum with VL and a good antigen to diagnose the visceral form in dogs. Here, we show that the LinJ.30.3360 protein is conserved in L. infantum, L. tarantolae, L. donovani, L. major, L. mexicana, L. braziliensis, L. panamensis, Leptomonas pyrrhocoris, and Leptomonas seymouri. It has been annotated as a MORN (Membrane Occupation and Recognition Nexus) domain protein. However, since the function of this motif is unknown, functional inferences based on the primary sequence are not possible. The protein has a folded β-leaf secondary structure, and phosphorylation was the only post-translational modification (PTM) found using prediction approach. Experiments have shown that it is located close to the flagellar pocket and presents similar abundance in both L. amazonensis and L. infantum. Furthermore, because it is a conserved protein in trypanosomatids but not in mammals and also because of its antigenicity, LinJ.30.3360 may constitute a potential drug target and/or vaccine for leishmaniasis.
利什曼病是一种由锥体虫原生动物属利什曼原虫引起的疾病。在美洲，物种利什曼原虫亚马逊亚种主要与美洲皮肤利什曼病（ACL）相关，而利什曼原虫婴儿亚种是内脏利什曼病（VL）的病原体。利什曼原虫物种的基因组序列表明，每个基因组可以包含约 8000 个编码蛋白质的基因，其中一半以上在发表时具有未知功能（“假设”）。为了了解生物体的生物学和基因组，发现这些“假设”蛋白质的功能非常重要；然而，很少有研究关注它们的特征。以前，LinJ.30.3360（一种未知功能的蛋白质）被鉴定为患有 VL 的犬血清中的免疫原性，并且是诊断犬内脏形式的良好抗原。在这里，我们表明，LinJ.30.3360 蛋白在利什曼原虫婴儿亚种、利什曼原虫 tarantolae、利什曼原虫婴儿亚种、利什曼原虫 major、利什曼原虫 mexicana、利什曼原虫 braziliensis、利什曼原虫 panamensis、Leptomonas pyrrhocoris 和 Leptomonas seymouri 中保守。它被注释为 MORN（膜占领和识别连接）结构域蛋白。然而，由于该结构域的功能未知，基于一级序列的功能推断是不可能的。该蛋白具有折叠的β-页二级结构，并且使用预测方法仅发现了磷酸化这一种翻译后修饰（PTM）。实验表明，它位于鞭毛口袋附近，在利什曼原虫亚马逊亚种和利什曼原虫婴儿亚种中丰度相似。此外，由于它是锥体虫中的保守蛋白，但不是哺乳动物中的保守蛋白，并且由于其抗原性，LinJ.30.3360 可能构成利什曼病的潜在药物靶点和/或疫苗。
