Dataset Information

Role of malectin in Glc(2)Man(9)GlcNAc(2)-dependent quality control of ?1-antitrypsin.

ABSTRACT: Malectin was first discovered as a novel endoplasmic reticulum (ER)-resident lectin from Xenopus laevis that exhibits structural similarity to bacterial glycosylhydrolases. Like other intracellular lectins involved in glycoprotein quality control, malectin is highly conserved in animals. Here results from in vitro membrane-based binding assays and frontal affinity chromatography confirm that human malectin binds specifically to Glc(2)Man(9)GlcNAc(2) (G2M9) N-glycan, with a K(a) of 1.97 × 10(5) M(-1), whereas binding to Glc(1)Man(9)GlcNAc(2) (G1M9), Glc(3)Man(9)GlcNAc(2) (G3M9), and other N-glycans is barely detectable. Metabolic labeling and immunoprecipitation experiments demonstrate that before entering the calnexin cycle, the folding-defective human ?1-antitrypsin variant null Hong Kong (AT(NHK)) stably associates with malectin, whereas wild-type ?1-antitrypsin (AT) or N-glycan-truncated variant of AT(NHK) (AT(NHK)-Q3) dose not. Moreover, malectin overexpression dramatically inhibits the secretion of AT(NHK) through a mechanism that involves enhanced ER-associated protein degradation; by comparison, the secretion of AT and AT(NHK)-Q3 is only slightly affected by malectin overexpression. ER-stress induced by tunicamycin results in significantly elevated mRNA transcription of malectin. These observations suggest a possible role of malectin in regulating newly synthesized glycoproteins via G2M9 recognition.

SUBMITTER: Chen Y

PROVIDER: S-EPMC3183012 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Role of malectin in Glc(2)Man(9)GlcNAc(2)-dependent quality control of α1-antitrypsin.

Chen Yang Y Hu Dan D Yabe Rikio R Tateno Hiroaki H Qin Sheng-Ying SY Matsumoto Naoki N Hirabayashi Jun J Yamamoto Kazuo K

Molecular biology of the cell 20110803 19

Malectin was first discovered as a novel endoplasmic reticulum (ER)-resident lectin from Xenopus laevis that exhibits structural similarity to bacterial glycosylhydrolases. Like other intracellular lectins involved in glycoprotein quality control, malectin is highly conserved in animals. Here results from in vitro membrane-based binding assays and frontal affinity chromatography confirm that human malectin binds specifically to Glc(2)Man(9)GlcNAc(2) (G2M9) N-glycan, with a K(a) of 1.97 × 10(5) M ...[more]

PMID: 21813736

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Dataset Information

Role of malectin in Glc(2)Man(9)GlcNAc(2)-dependent quality control of ?1-antitrypsin.

Publications

Role of malectin in Glc(2)Man(9)GlcNAc(2)-dependent quality control of α1-antitrypsin.

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