Histidines in the octapeptide repeat of PrPC react with PrPSc at an acidic pH.
Histidines in the octapeptide repeat of PrPC react with PrPSc at an acidic pH.
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PrPC 八肽重复序列中的组氨酸在酸性 pH 条件下与 PrPSc 发生反应。
DOI：
10.1021/bi1017683
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发表时间：
2011
期刊：
影响因子：
2.9
通讯作者：
Solforosi,Laura
中科院分区：
文献类型：
--
作者：
Cruite,JustinT;Abalos,GilC;Bellon,Anne;Solforosi,Laura
细胞PrP在细胞表面和内体途径之间活跃循环。从prpc到prpscreen转换的确切位置和机制尚不清楚。我们以前使用含有PrP序列移植物的重组抗体来鉴定PrPC的三个区域（aa23−27,98−110和136−158）在中性pH下与PrPScat反应。为了确定PrPScat的酸性pH是否与内体腔室相似，我们测试了我们的移植抗体在一系列pH条件下沉淀PrPScat的能力。在pH接近或低于6时，代表八肽重复的prp嫁接抗体与prpsct而不是PrPC发生强烈反应。用丙氨酸取代八萜组氨酸的修饰移植物与PrPSc不发生反应。在ph5.7条件下，八肽沉淀的PrP能够在体外将正常PrP转化为PrPScin。然而，在八肽重复序列中含有组氨酸到丙氨酸取代的修饰PrP仍然转化为PrPScin N2a细胞。这些结果表明，一旦PrP进入内体途径，酸性环境通过改变八联体内组氨酸的控制，促进了prpsct与prpsct的结合。
Cellular PrP is actively cycled between the cell surface and the endosomal pathway. The exact site and mechanism of conversion from PrPCto PrPScremain unknown. We have previously used recombinant antibodies containing grafts of PrP sequence to identify three regions of PrPC(aa23−27, 98−110, and 136−158) that react with PrPScat neutral pH. To determine if any regions of PrPCreact with PrPScat an acidic pH similar to that of an endosomal compartment, we tested our panel of grafted antibodies for the ability to precipitate PrPScin a range of pH conditions. At pH near or lower than 6, PrP-grafted antibodies representing the octapeptide repeat react strongly with PrPScbut not PrPC. Modified grafts in which the histidines of the octarepeat were replaced with alanines did not react with PrPSc. PrPScprecipitated by the octapeptide at pH 5.7 was able to seed conversion of normal PrP to PrPScin vitro. However, modified PrP containing histidine to alanine substitutions within the octapeptide repeats was still converted to PrPScin N2a cells. These results suggest that once PrP has entered the endosomal pathway, the acidic environment facilitates the binding of PrPScto the octarepeat of PrPCby the change in charge of the histidines within the octarepeat.