Soldà Tatiana, Galli Carmela, Kaufman Randal J, Molinari Maurizio
Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland.
Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, MI 48109, USA; Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
Mol Cell. 2007 Jul 20;27(2):238-249. doi: 10.1016/j.molcel.2007.05.032.
Newly synthesized glycoproteins displaying monoglucosylated N-glycans bind to the endoplasmic reticulum (ER) chaperone calnexin, and their maturation is catalyzed by the calnexin-associated oxidoreductase ERp57. Folding substrates are eventually released from calnexin, and terminal glucoses are removed from N-glycans. The UDP-glucose:glycoprotein glucosyltransferase (UGT1, UGGT, GT) monitors the folding state of polypeptides released from calnexin and adds back a glucose residue on N-glycans of nonnative polypeptides, thereby prolonging retention in the calnexin chaperone system for additional folding attempts. Here we show that for certain newly synthesized glycoproteins UGT1 deletion has no effect on binding to calnexin. These proteins must normally complete their folding program in one binding event. Other proteins normally undergo multiple binding events, and UGT1 deletion results in their premature release from calnexin. For other proteins, UGT1 deletion substantially delays release from calnexin, unexpectedly showing that UGT1 activity might be required for a structural maturation needed for substrate dissociation from calnexin and export from the ER.
新合成的展示单葡糖基化N-聚糖的糖蛋白与内质网（ER）伴侣钙连蛋白结合，其成熟由与钙连蛋白相关的氧化还原酶ERp57催化。折叠底物最终从钙连蛋白上释放，N-聚糖上的末端葡萄糖被去除。UDP-葡萄糖：糖蛋白葡糖基转移酶（UGT1、UGGT、GT）监测从钙连蛋白释放的多肽的折叠状态，并在非天然多肽的N-聚糖上重新添加一个葡萄糖残基，从而延长其在钙连蛋白伴侣系统中的保留时间，以便进行额外的折叠尝试。在这里，我们表明，对于某些新合成的糖蛋白，UGT1缺失对与钙连蛋白的结合没有影响。这些蛋白质通常必须在一次结合事件中完成其折叠程序。其他蛋白质通常经历多次结合事件，UGT1缺失导致它们从钙连蛋白过早释放。对于其他蛋白质，UGT1缺失会显著延迟从钙连蛋白的释放，出乎意料地表明UGT1活性可能是底物从钙连蛋白解离并从内质网输出所需的结构成熟所必需的。
