Malectin: A Novel Carbohydrate-binding Protein of the Endoplasmic Reticulum and a Candidate Player in the Early Steps of ProteinN-Glycosylation

Abstract

N-Glycosylation starts in the endoplasmic reticulum (ER) where a 14-sugar glycan composed of three glucoses, nine mannoses, and two N-acetylglucosamines (Glc(3)Man(9)GlcNAc(2)) is transferred to nascent proteins. The glucoses are sequentially trimmed by ER-resident glucosidases. The Glc(3)Man(9)GlcNAc(2) moiety is the substrate for oligosaccharyltransferase; the Glc(1)Man(9)GlcNAc(2) and Man(9)GlcNAc(2) intermediates are signals for glycoprotein folding and quality control in the calnexin/calreticulin cycle. Here, we report a novel membrane-anchored ER protein that is highly conserved in animals and that recognizes the Glc(2)-N-glycan. Structure determination by nuclear magnetic resonance showed that its luminal part is a carbohydrate binding domain that recognizes glucose oligomers. Carbohydrate microarray analyses revealed a uniquely selective binding to a Glc(2)-N-glycan probe. The localization, structure, and binding specificity of this protein, which we have named malectin, open the way to studies of its role in the genesis, processing and secretion of N-glycosylated proteins.

Protein Folding in the Endoplasmic Reticulum

“…2) (Hubbard and Robbins 1979;Lehrman 2001). Furthermore, malectin, an ER lectin, was recently characterized and shown to bind specifically to proteins possessing diglucosylated glycans (Schallus et al 2008). As this glycan composition is generally present at early stages during the cotranslational program, this suggests that malectin is involved in early maturation steps.…”

Malectin Forms a Complex with Ribophorin I for Enhanced Association with Misfolded Glycoproteins

“…Because malectin, a novel ER-resident protein, was first reported by the Xenopus laevis proteomic study, its selective binding to di-glucosylated high mannose-type N-glycans has led to much speculation regarding its function (12,13). By analogy with the mono-glucosylated N-glycan-binding lectins, CNX and CRT, which play an essential role in the folding of glycoproteins, malectin is also suggested to be involved in the quality control of glycoproteins in the ER.…”

“…Malectin does not have an ER localization signal in its molecule, although it localizes in the ER. Schallus et al (12) proposed that malectin would associate with other ER-resident protein(s) to keep its localization in the ER. Our finding may explain malectin localization in the ER because ribophorin I has ER retention signal in its cytoplasmic domain.…”

RLKs orchestrate the signaling in plant male-female interaction

“…It was proposed that ANX and the CrRLK1L family, as a signaling integrator, could sense the cell wall integrity simultaneously (Cheung and Wu, 2011;Lindner et al, 2012). The CrRLK1L family contains two malectin-like domains at the extracellular region sharing limited homology with the animal endoplasmic reticulum-localized malectin that bind di-glucose (Schallus et al, 2008). This sequence similarity is indicative of a cell wall binding potential of the family.…”