The structure of a Plasmodium vivax Tryptophan Rich Antigen domain suggests a lipid binding function for a pan-Plasmodium multi-gene family.
The structure of a Plasmodium vivax Tryptophan Rich Antigen domain suggests a lipid binding function for a pan-Plasmodium multi-gene family.
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DOI：
10.1038/s41467-023-40885-8
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发表时间：
2023-09-14
影响因子：
16.6
通讯作者：
Rayner, Julian C.
中科院分区：
文献类型：
--
作者：
Kundu, Prasun;Naskar, Deboki;Mckie, Shannon J.;Dass, Sheena;Kanjee, Usheer;Introini, Viola;Ferreira, Marcelo U.;Cicuta, Pietro;Duraisingh, Manoj;Deane, Janet E.;Rayner, Julian C.
富含色氨酸抗原（TRAgs）由一个多基因家族编码，存在于所有疟原虫物种中，但在间日疟原虫和与其密切相关的寄生虫中显著扩增。我们发现多个间日疟原虫的trg在子午线表面表达，其中一个PVP01_0000100结合了对网状红细胞有强烈偏好的红细胞。利用x射线晶体学，我们解析了定义TRAg家族的PVP01_0000100 c端色氨酸富结构域的结构，揭示了一个在疟原虫中保守的三螺旋束，并与参与膜重塑的脂质结合BAR结构域具有结构同源性。生化分析证实PVP01_0000100 c端结构域具有脂质结合活性，并优先与硫脂结合，这是一种存在于质膜外小叶的鞘糖脂。诺氏疟原虫推测的同源基因PKNH_1300500的缺失影响了网状红细胞的侵袭，表明其在这一重要过程中发挥了作用。总之，这项工作定义了疟原虫TRAg家族的新分子功能。虽然富含色氨酸抗原多基因家族（TRAgs）蛋白在任何疟原虫物种中的确切功能尚不清楚，但间日疟原虫TRAg家族的几个成员已被报道具有红细胞结合特性。这里，Kundu和Naskar等人提供了间日疟原虫PVP01_0000100的TRAg结构域的x射线晶体学结构。结构和生化分析表明一个泛疟原虫多基因家族具有脂质结合功能。
Tryptophan Rich Antigens (TRAgs) are encoded by a multi-gene family found in all Plasmodium species, but are significantly expanded in P. vivax and closely related parasites. We show that multiple P. vivax TRAgs are expressed on the merozoite surface and that one, PVP01_0000100 binds red blood cells with a strong preference for reticulocytes. Using X-ray crystallography, we solved the structure of the PVP01_0000100 C-terminal tryptophan rich domain, which defines the TRAg family, revealing a three-helical bundle that is conserved across Plasmodium and has structural homology with lipid-binding BAR domains involved in membrane remodelling. Biochemical assays confirm that the PVP01_0000100 C-terminal domain has lipid binding activity with preference for sulfatide, a glycosphingolipid present in the outer leaflet of plasma membranes. Deletion of the putative orthologue in P. knowlesi, PKNH_1300500, impacts invasion in reticulocytes, suggesting a role during this essential process. Together, this work defines an emerging molecular function for the Plasmodium TRAg family. Although the precise function of Tryptophan rich antigen multi-gene family (TRAgs) proteins is not known in any Plasmodium species several members of the P. vivax TRAg family have been reported to have red blood cell binding properties. Here, Kundu and Naskar et al. provide the X-ray crystallography structure of a P. vivax TRAg domain of PVP01_0000100. Structural and biochemical assays suggest a lipid binding function for a pan-Plasmodium multi-gene family.
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DOI：
10.1084/jem.174.5.1203
发表时间：
1991-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Barr PJ;Green KM;Gibson HL;Bathurst IC;Quakyi IA;Kaslow DC
通讯作者：
Kaslow DC
影响因子：
6.7
作者：
Collins CR;Hackett F;Strath M;Penzo M;Withers-Martinez C;Baker DA;Blackman MJ
通讯作者：
Blackman MJ
影响因子：
--
作者：
Auburn, Sarah;Bohme, Ulrike;Otto, Thomas D
通讯作者：
Otto, Thomas D
影响因子：
7.7
作者：
Dasanna AK;Hillringhaus S;Gompper G;Fedosov DA
通讯作者：
Fedosov DA
影响因子：
14.9
作者：
Dereeper A;Guignon V;Blanc G;Audic S;Buffet S;Chevenet F;Dufayard JF;Guindon S;Lefort V;Lescot M;Claverie JM;Gascuel O
通讯作者：
Gascuel O