The role of EDEM3, Derlin-1 and Derlin-2 proteins in the ricin P250A cytotoxicity and its retrotranslocation from the endoplasmic reticulum to the cytosol最新文献
ERAD-ER-associated degradation is a part of a protein quality control system operating in the endoplasmic reticulum (ER), which has an impact on process determining the proper functioning of all eukaryotic cells. Many of all newly synthesized proteins are produced in the ER. Some of them may fail to attain their native structure and have to be transported to the cytosol for proteasomal degradation (ERAD). The major group of chaperones which recognize terminally misfolded proteins is EDEM family (EDEM1, EDEM2, EDEM3) (Słomińska-Wojewódzka et al., 2006). The second type of proteins important in ERAD are Derlin family: Derlin-1, Derlin-2, and Derlin-3 which are thought to form a retrotranslocation channel (Oda et al., 2016). Ricin is a protein toxin that utilizes the ERAD pathway in its transport from the ER to the cytosol where it acts. It is heterodimeric holotoxin composed of an A-chain (RTA) connected to a cell binding lectin B-chain (RTB). RTA contains hydrophobic C-terminal region. Substitution of proline into alanine in position 250 (P250A) of this region alters the secondary structure of ricin and decreases its cytotoxicity (Słomińska-Wojewódzka & Sandvig, 2013).
erder -ER相关降解是内质网(ER)中蛋白质质量控制系统的一部分，它对决定所有真核细胞正常功能的过程产生影响。许多新合成的蛋白质都是在内质网中产生的。其中一些可能无法达到其天然结构，必须被运输到细胞质中进行蛋白酶体降解(ERAD)。识别最终错误折叠蛋白的伴侣蛋白主要是EDEM家族(EDEM1, EDEM2, EDEM3) (Słomińska-Wojewódzka et al.， 2006)。ERAD中第二种重要的蛋白质是Derlin家族:Derlin-1、Derlin-2和Derlin-3，它们被认为形成了一个逆转录易位通道(Oda et al.， 2016)。蓖麻毒素是一种蛋白质毒素，利用ERAD途径从内质网运输到它起作用的细胞质。它是一种异二聚体全毒素，由a链(RTA)连接到细胞结合凝集素b链(RTB)组成。RTA含有疏水c端区。脯氨酸在该区域250位(P250A)取代丙氨酸改变了蓖麻毒素的二级结构，降低了其细胞毒性(Słomińska-Wojewódzka & Sandvig, 2013)。
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The role of EDEM3, Derlin-1 and Derlin-2 proteins in the ricin P250A cytotoxicity and its retrotranslocation from the endoplasmic reticulum to the cytosol
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