Mapping the ER Interactome: The P Domains of Calnexin and Calreticulin as Plurivalent Adapters for Foldases and Chaperones
Mapping the ER Interactome: The P Domains of Calnexin and Calreticulin as Plurivalent Adapters for Foldases and Chaperones
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DOI：
10.1016/j.str.2017.07.010
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发表时间：
2017-09-05
期刊：
影响因子：
5.7
通讯作者：
Gehring, Kalle
中科院分区：
文献类型：
--
作者：
Kozlov, Guennadi;Munoz-Escobar, Juliana;Gehring, Kalle
凝集素伴侣钙网蛋白（CRT）和钙连接蛋白（CNX）通过募集折叠酶（如蛋白质二硫键异构酶ERp 57和肽基脯氨酰顺反异构酶CypB）促进ER中糖蛋白的折叠。最近，CRT显示与伴侣ERp 29相互作用。在这里，我们表明，ERp 29直接结合到CNX的P结构域。ERp 29的D结构域与CRT和calmegin（一种组织特异性CNX同系物）的P结构域复合的晶体结构揭示了结合机制的共同性，其中P结构域的尖端作为多价接头发挥作用以结合多种折叠因子。我们发现，CNX中的单个残基D348的突变废除了与ERp 29以及ERp 57和CypB的结合。辅助因子的结构多样性表明，这些分子伴侣通过其P-结构域结合位点的趋同进化而专门用于糖蛋白折叠。
The lectin chaperones calreticulin (CRT) and calnexin (CNX) contribute to the folding of glycoproteins in the ERby recruiting foldases such as the protein disulfide isomerase ERp57 and the peptidyl prolyl cis-trans isomerase CypB. Recently, CRT was shown to interact with the chaperone ERp29. Here, we show that ERp29 directly binds to the P domain of CNX. Crystal structures of the D domain of ERp29 in complex with the P domains from CRT and calmegin, a tissue-specific CNX homolog, reveal a commonality in the mechanism of binding whereby the tip of the P domain functions as a plurivalent adapter to bind a variety of folding factors. We show that mutation of a single residue, D348 in CNX, abrogates binding to ERp29 as well as ERp57 and CypB. The structural diversity of the accessory factors suggests that these chaperones became specialized for glycoprotein folding through convergent evolution of their P-domain binding sites.