Glycosylphosphatidylinositol-anchored micronemal antigen (GAMA) interacts with the band 3 receptor to promote erythrocyte invasion by malaria parasites.
Glycosylphosphatidylinositol-anchored micronemal antigen (GAMA) interacts with the band 3 receptor to promote erythrocyte invasion by malaria parasites.
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糖基磷脂酰肌醇锚定的微线抗原 (GAMA) 与带 3 受体相互作用，促进疟疾寄生虫对红细胞的侵袭
DOI：
10.1016/j.jbc.2022.101765
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发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
Cheng Y
中科院分区：
文献类型：
--
作者：
Lu J;Chu R;Yin Y;Yu H;Xu Q;Yang B;Sun Y;Song J;Wang Q;Xu J;Lu F;Cheng Y
糖基磷脂酰肌醇锚定微囊抗原（GAMA）是一种已知参与疟疾寄生虫侵袭的红细胞结合蛋白。虽然抗GAMA抗体已被证明可以阻断GAMA附着在红细胞表面并随后抑制寄生虫的入侵，但对于GAMA促进入侵过程的分子机制知之甚少。在这项研究中，LC-MS分析在红细胞膜上进行，以确定与GAMA相互作用的特异性受体。我们发现锚蛋白1和带3膜蛋白对GAMA具有亲和力，并且它们的结合特异性表征表明，恶性疟原虫和间日疟原虫GAMA都结合在带3的同一个细胞外环（环5）上。此外，我们发现GAMA和能带3之间的相互作用对凝乳胰蛋白酶敏感。此外，抗带3环5的抗体能够降低GAMA与红细胞的结合活性，抑制恶性疟原虫merozoites入侵人红细胞，而抗恶性疟原虫GAMA (PfGAMA)-Tr3抗体仅能轻微降低恶性疟原虫的入侵。红细胞GAMA受体的鉴定和表征是一项新的发现，它确定了寄生虫入侵宿主红细胞的基本机制。
Glycosylphosphatidylinositol-anchored micronemal antigen (GAMA) is an erythrocyte binding protein known to be involved in malarial parasite invasion. Although anti-GAMA antibodies have been shown to block GAMA attachment to the erythrocyte surface and subsequently inhibit parasite invasion, little is known about the molecular mechanisms by which GAMA promotes the invasion process. In this study, LC-MS analysis was performed on the erythrocyte membrane to identify the specific receptor that interacts with GAMA. We found that ankyrin 1 and the band 3 membrane protein showed affinity for GAMA, and characterization of their binding specificity indicated that both Plasmodium falciparum and Plasmodium vivax GAMA bound to the same extracellular loop of band 3 (loop 5). In addition, we show the interaction between GAMA and band 3 was sensitive to chymotrypsin. Furthermore, antibodies against band 3 loop 5 were able to reduce the binding activity of GAMA to erythrocytes and inhibit the invasion of P. falciparum merozoites into human erythrocytes, whereas antibodies against P. falciparum GAMA (PfGAMA)-Tr3 only slightly reduced P. falciparum invasion. The identification and characterization of the erythrocyte GAMA receptor is a novel finding that identifies an essential mechanism of parasite invasion of host erythrocytes.
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影响因子：
4.6
作者：
Cheng Y;Lu F;Wang B;Li J;Han JH;Ito D;Kong DH;Jiang L;Wu J;Ha KS;Takashima E;Sattabongkot J;Cao J;Nyunt MH;Kyaw MP;Desai SA;Miller LH;Tsuboi T;Han ET
通讯作者：
Han ET
DOI：
10.1073/pnas.1104050108
发表时间：
2011-05-03
影响因子：
11.1
作者：
Jiang, Lubin;Gaur, Deepak;Miller, Louis H.
通讯作者：
Miller, Louis H.
影响因子：
20.3
作者：
Almukadi, Haifa;Schwake, Christopher;Chishti, Athar H.
通讯作者：
Chishti, Athar H.
影响因子：
64.8
作者：
Crosnier, Cecile;Bustamante, Leyla Y.;Bartholdson, S. Josefin;Bei, Amy K.;Theron, Michel;Uchikawa, Makoto;Mboup, Souleymane;Ndir, Omar;Kwiatkowski, Dominic P.;Duraisingh, Manoj T.;Rayner, Julian C.;Wright, Gavin J.
通讯作者：
Wright, Gavin J.
影响因子：
3.9
作者：
DODGE, JT;HANAHAN, DJ;MITCHELL, C
通讯作者：
MITCHELL, C