Tannous Abla, Pisoni Giorgia Brambilla, Hebert Daniel N, Molinari Maurizio
Department of Biochemistry and Molecular Biology, Program in Molecular and Cellular Biology, University of Massachusetts, Amherst, MA 01003, USA.
Università della Svizzera italiana, CH-6900 Lugano, Switzerland.
Semin Cell Dev Biol. 2015 May;41:79-89. doi: 10.1016/j.semcdb.2014.12.001. Epub 2014 Dec 19.
Asparagine-linked glycans (N-glycans) are displayed on the majority of proteins synthesized in the endoplasmic reticulum (ER). Removal of the outermost glucose residue recruits the lectin chaperone malectin possibly involved in a first triage of defective polypeptides. Removal of a second glucose promotes engagement of folding and quality control machineries built around the ER lectin chaperones calnexin (CNX) and calreticulin (CRT) and including oxidoreductases and peptidyl-prolyl isomerases. Deprivation of the last glucose residue dictates the release of N-glycosylated polypeptides from the lectin chaperones. Correctly folded proteins are authorized to leave the ER. Non-native polypeptides are recognized by the ER quality control key player UDP-glucose glycoprotein glucosyltransferase 1 (UGT1), re-glucosylated and re-addressed to the CNX/CRT chaperone binding cycle to provide additional opportunity for the protein to fold in the ER. Failure to attain the native structure determines the selection of the misfolded polypeptides for proteasome-mediated degradation.
天冬酰胺连接聚糖（N-聚糖）存在于在内质网（ER）中合成的大多数蛋白质上。去除最外层的葡萄糖残基会招募凝集素伴侣分子Malectin，它可能参与对有缺陷多肽的初步分类。去除第二个葡萄糖会促进围绕内质网凝集素伴侣分子钙连蛋白（CNX）和钙网蛋白（CRT）构建的折叠和质量控制机制的参与，这些机制还包括氧化还原酶和肽基脯氨酰异构酶。去除最后一个葡萄糖残基会促使N-糖基化多肽从凝集素伴侣分子上释放。正确折叠的蛋白质被允许离开内质网。非天然多肽被内质网质量控制的关键参与者UDP-葡萄糖糖蛋白糖基转移酶1（UGT1）识别，重新糖基化并重新进入CNX/CRT伴侣分子结合循环，为蛋白质在内质网中折叠提供额外机会。未能达到天然结构会导致选择错误折叠的多肽进行蛋白酶体介导的降解。
