Max Planck Institute for Infection Biology, Berlin, Germany.
European Molecular Biology Laboratory, Hamburg Unit, Hamburg, Germany.
Front Cell Infect Microbiol. 2022 Jun 24;12:926541. doi: 10.3389/fcimb.2022.926541. eCollection 2022.
Malaria remains a leading cause of death and disease in many tropical and subtropical regions of the world. Due to the alarming spread of resistance to almost all available antimalarial drugs, novel therapeutic strategies are urgently needed. As the intracellular human malaria parasite depends entirely on the host to meet its nutrient requirements and the majority of its transmembrane transporters are essential and lack human orthologs, these have often been suggested as potential targets of novel antimalarial drugs. However, membrane proteins are less amenable to proteomic tools compared to soluble parasite proteins, and have thus not been characterised as well. While it had been proposed that had a lower number of transporters (2.5% of its predicted proteome) in comparison to most reference genomes, manual curation of information from various sources led to the identification of 197 known and putative transporter genes, representing almost 4% of all parasite genes, a proportion that is comparable to well-studied metazoan species. This transporter list presented here was compiled by collating data from several databases along with extensive literature searches, and includes parasite-encoded membrane-resident/associated channels, carriers, and pumps that are located within the parasite or exported to the host cell. It provides updated information on the substrates, subcellular localisation, class, predicted essentiality, and the presence or absence of human orthologs of transporters to quickly identify essential proteins without human orthologs for further functional characterisation and potential exploitation as novel drug targets.
疟疾仍然是世界上许多热带和亚热带地区主要的死亡和疾病原因。由于几乎所有现有的抗疟药物的耐药性都在令人震惊地传播，因此迫切需要新的治疗策略。由于人体疟原虫完全依赖宿主来满足其营养需求，并且其大多数跨膜转运蛋白都是必需的且缺乏人类同源物，因此这些通常被认为是潜在的新型抗疟药物靶点。然而，与可溶性寄生虫蛋白相比，膜蛋白不太适合蛋白质组学工具，因此它们的特征也不太好。尽管有人提出与大多数参考基因组相比， 的转运蛋白数量较少（占其预测蛋白质组的 2.5%），但从各种来源手动整理信息导致鉴定出 197 个已知和推定的转运基因，代表几乎所有寄生虫基因的 4%，这一比例与研究充分的后生动物物种相当。这里呈现的转运蛋白列表是通过从几个数据库中整理数据以及广泛的文献检索来编制的，其中包括位于寄生虫内或输出到宿主细胞的寄生虫编码的膜驻留/相关通道、载体和泵。它提供了有关转运蛋白的底物、亚细胞定位、类别、预测的必需性以及人类同源物的存在或缺失的最新信息，以便快速识别没有人类同源物的必需蛋白，以便进一步进行功能表征，并可能将其作为新型药物靶点进行开发。
