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Vol. 19, Issue 8, 3404-3414, August 2008

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

Thomas Schallus^*,, Christine Jaeckh^,, Krisztina Fehér^*,,, Angelina S. Palma^||, Yan Liu^||, Jeremy C. Simpson^*, Mukram Mackeen^¶, Gunter Stier^*,#, Toby J. Gibson^*, Ten Feizi^||, Tomas Pieler, and Claudia Muhle-Goll^*,,@

*European Molecular Biology Laboratory, 69117 Heidelberg, Germany; Max-Planck-Institut for Medical Research, 69120 Heidelberg, Germany; Department of Developmental Biochemistry und University Medical Center Göttingen, 37077 Göttingen, Germany; ^||The Glycosciences Laboratory, Faculty of Medicine, Imperial College London, Northwick Park and St. Mark's Hospital Campus, Harrow, Middlesex HA1 3UJ, United Kingdom; and ^¶Oxford Glycobiology Institute, University of Oxford, Oxford OX1 3QU, United Kingdom

Submitted April 6, 2008; Revised May 9, 2008; Accepted May 28, 2008
Monitoring Editor: Reid Gilmore

N-Glycosylation starts in the endoplasmic reticulum (ER) where a 14-sugar glycan composed of three glucoses, nine mannoses, and two N-acetylglucosamines (Glc₃Man₉GlcNAc₂) is transferred to nascent proteins. The glucoses are sequentially trimmed by ER-resident glucosidases. The Glc₃Man₉GlcNAc₂ moiety is the substrate for oligosaccharyltransferase; the Glc₁Man₉GlcNAc₂ and Man₉GlcNAc₂ 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 Glc₂-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 Glc₂-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.

These authors contributed equally to this work.

Present addresses: ^# Umeå Center for Molecular Pathogenesis, Umeå University, SE-90187 Umeå, Sweden;

^@ Karlsruhe Institute of Technology (KIT), Institut für biologische Grenzflächen (IBG-2), POB 3640, 76021 Karlsruhe, Germany.

Address correspondence to: Claudia Muhle-Goll (claudia.muhle{at}kit.edu)

Abbreviations used: CBM, carbohydrate binding module; ER, endoplasmic reticulum; GII, glucosidase II; RLK, receptor like kinase; STD, saturation transference difference.