Malectin: a novel carbohydrate-binding protein of the endoplasmic reticulum and a candidate player in the early steps of protein N-glycosylation.
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.
Schallus
Thomas
T
European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
Jaeckh
Christine
C
Fehér
Krisztina
K
Palma
Angelina S
AS
Liu
Yan
Y
Simpson
Jeremy C
JC
Mackeen
Mukram
M
Stier
Gunter
G
Gibson
Toby J
TJ
Feizi
Ten
T
Pieler
Tomas
T
Muhle-Goll
Claudia
C
D000595:Amino Acid Sequence; D000818:Animals; D037281:Calnexin / Q000737:chemistry; D037282:Calreticulin / Q000737:chemistry; D002241:Carbohydrates / Q000737:chemistry*; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D037102:Lectins / Q000737:chemistry / Q000502:physiology*; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology*; D008954:Models, Biological; D008969:Molecular Sequence Data; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D014982:Xenopus laevis
D037282:Calreticulin; D002241:Carbohydrates; D037102:Lectins; C533791:MLEC protein, Xenopus; D008565:Membrane Proteins; D037281:Calnexin