Department of Pharmacology, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife 220005, Nigeria.
Department of Bioinformatics, Hans Raj Mahila Maha Vidyalaya, Jalandhar 144008, India.
Int J Mol Sci. 2024 Nov 16;25(22):12302. doi: 10.3390/ijms252212302.
is a zoonotic form of human malaria, the pathology of which is poorly understood. While the J domain protein (JDP) family has been extensively studied in , and shown to contribute to malaria pathology, there is currently very limited information on the JDPs (PkJDPs). This review provides a critical analysis of the literature and publicly available data on PkJDPs. Interestingly, the genome encodes at least 31 PkJDPs, with well over half belonging to the most diverse types which contain only the signature J domain (type IIIs, 19) or a corrupted version of the J domain (type IVs, 2) as evidence of their membership. The more typical PkJDPs containing other domains typical of JDPs in addition to the J domain are much fewer in number (type IIs, 8; type Is, 2). This study indentifies PkJDPs that are potentially involved in: folding of newly synthesized or misfolded proteins within the cytosol (a canonical type I and certain typical type IIs); protein translocation (a type III) and folding (a type II) in the ER; and protein import into mitochondria (a type III). Interestingly, a type II PkJDP is potentially exported to the host cell cytosol where it may recruit human HSP70 for the trafficking and folding of other exported proteins. Experimental studies are required on this fascinating family of proteins, not only to validate their role in the pathology of knowlesi malaria, but also because they represent potential anti-malarial drug targets.
是一种人畜共患的人类疟疾形式，其病理学尚不清楚。虽然 J 结构域蛋白（JDP）家族在 中已被广泛研究，并被证明有助于疟疾病理学，但目前关于 JDPs（PkJDPs）的信息非常有限。本综述对 PkJDPs 的文献和公开数据进行了批判性分析。有趣的是， 基因组至少编码 31 种 PkJDPs，其中超过一半属于最具多样性的类型，仅包含特征性的 J 结构域（III 型，19 种）或 J 结构域的篡改版本（IV 型，2 种），作为其成员的证据。更典型的 PkJDPs 除了 J 结构域外，还包含 JDP 中常见的其他结构域，数量要少得多（II 型，8 种；I 型，2 种）。本研究鉴定出可能参与以下过程的 PkJDPs：在 细胞质内折叠新合成或错误折叠的蛋白质（一种典型的 I 型和某些典型的 II 型）；内质网中的蛋白质易位（III 型）和折叠（II 型）；以及线粒体中的蛋白质导入（III 型）。有趣的是，一种 II 型 PkJDP 可能被输出到宿主细胞质中，在那里它可能招募人类 HSP70 用于其他输出 蛋白质的运输和折叠。需要对这一迷人的蛋白家族进行实验研究，不仅是为了验证它们在 knowlesi 疟疾病理学中的作用，还因为它们代表了潜在的抗疟药物靶点。
