Lectin chaperones help direct the maturation of glycoproteins in the endoplasmic reticulum

Abstract

Eukaryotic secretory pathway cargo fold to their native structures within the confines of the endoplasmic reticulum (ER). To ensure a high degree of folding fidelity, a multitude of covalent and noncovalent constraints are imparted upon nascent proteins. These constraints come in the form of topological restrictions or membrane tethers, covalent modifications, and interactions with a series of molecular chaperones. N-linked glycosylation provides inherent benefits to proper folding, and creates a platform for interactions with specific chaperones and Cys modifying enzymes. Recent insights into this timeline of protein maturation have revealed mechanisms for protein glycosylation, and iterative targeting of incomplete folding intermediates, which provides nurturing interactions with molecular chaperones that assist in the efficient maturation of proteins in the eukaryotic secretory pathway.

TMTC1 and TMTC2 Are Novel Endoplasmic Reticulum Tetratricopeptide Repeat-containing Adapter Proteins Involved in Calcium Homeostasis

“…TMTC2, but not TMTC1, interacted with calnexin. Calnexin is a carbohydrate-binding chaperone of the ER membrane that associates with maturing glycoproteins that possess monoglucosylated glycans (34). The TMTC2-calnexin interaction appeared to be specific because TMTC2 did not interact with calreticulin, the soluble paralog of calnexin, or the calnexinassociated oxidoreductase ERp57 (Fig.…”

Intracellular Cysteine 346 Is Essentially Involved in Regulating Panx1 Channel Activity

“…Interdependence of glycosylation and proper folding for interaction with chaperones and cysteine-modifying enzymes has been described frequently (for review, see Ref. 46). Lack of a cysteine at this particular position could compromise glycosylation capability of this protein.…”

Mixed disulfide formation in vitro between a glycoprotein substrate and yeast oligosaccharyltransferase subunits Ost3p and Ost6p

“…In eukaryotes, nascent polypeptide is N-glycosylated by the enzyme oligosaccharyltransferase (OTase) after entry into the endoplasmic reticulum (ER) lumen through the translocon [4,5,6]. N-glycans enhance the efficiency of glycoprotein folding in the ER by increasing the solubility of folding nascent polypeptide and by recruiting the disulfide isomerase ERp57 through the lectins calnexin and calreticulin [7,8,9,10]. Glycan structures are modified during glycoprotein traffic through the Golgi, and the final structures present on mature glycoproteins can play important roles in regulating protein function [1,11].…”