Extracellular lysines on the plasmodial surface anion channel involved in Na+ exclusion
Extracellular lysines on the plasmodial surface anion channel involved in Na+ exclusion
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DOI：
10.1016/j.molbiopara.2003.08.001
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发表时间：
2003-11-01
影响因子：
1.5
通讯作者：
Desai, SA
中科院分区：
文献类型：
--
作者：
Cohn, JV;Alkhalil, A;Desai, SA
人类疟疾寄生虫，恶性疟原虫，诱导一个不寻常的离子通道，疟原虫表面阴离子通道（PSAC），在其宿主红细胞（RBC）膜。PSAC具有广泛的选择性，对阴离子、糖、氨基酸、嘌呤和某些维生素具有渗透性，表明其在细胞内寄生虫的营养获取中起作用。渗透性溶质涵盖一系列分子大小，并且可以是中性的或携带净负电荷或正电荷。尽管有这种广泛的选择性，PSAC必须有效地排除Na+，以避免血流中受感染的RBC的渗透溶解。在这里，我们使用胺反应性N-羟基磺基琥珀酰亚胺酯来探测PSAC的不寻常的选择性。PSAC的渗透率，测定与动力学渗透溶解试验和单通道膜片钳，不可逆地减少后，这些试剂的治疗。顺序标记不同的酯和它们的链长的影响表明，PSAC有多个赖氨酸残基附近的细胞外孔的嘴和抑制发生通过空间位阻其孔由酰胺连接的侧链。当结合pH值对渗透的影响，这些研究结果暗示的结合阳离子排斥的孔隙口电荷和渗透溶质在PSAC的广泛的选择性，但有效的排除Na+的弱结合位点。2003 Elsevier B. V.保留所有权利。
The human malaria parasite, Plasmodium falciparum, induces an unusual ion channel, the plasmodial surface anion channel (PSAC), on its host red blood cell (RBC) membrane. PSAC has a broad selectivity with permeability to anions, sugars, amino acids, purines, and certain vitamins, suggesting a role in nutrient acquisition by the intracellular parasite. Permeating solutes cover a range of molecular sizes and may be either neutral or carry a net negative or positive charge. Despite this broad selectivity, PSAC must efficiently exclude Na+ to avoid osmotic lysis of infected RBCs in the bloodstream. Here, we used amine-reactive N-hydroxysulfosuccinimide esters to probe PSAC's unusual selectivity. PSAC permeation rates, measured with both a kinetic osmotic lysis assay and single-channel patch-clamp, irreversibly decrease after treatment with these reagents. Sequential labelings with different esters and the effects of their chain length suggest that PSAC has multiple lysine residues near its extracellular pore mouth and that inhibition occurs via steric hindrance of its pore by the amide-linked side chain. When combined with the effects of pH on permeation, these findings implicate a combination of cation repulsion by pore mouth charges and a weak binding site for permeant solutes in PSAC's broad selectivity yet effective exclusion of Na+. 2003 Elsevier B.V. All rights reserved.