Molecular cloning and characterization of a novel human  1,3-glucosyltransferase, which is localized at the endoplasmic reticulum and glucosylates O-linked fucosylglycan on thrombospondin type 1 repeat domain

Sato, Takashi; Sato, Masamichi; Kiyohara, Katsue; Sogabe, Masamichi; Shikanai, Toshihide; Kikuchi, Norihiro; Togayachi, Akira; Ishida, Hiroyasu; Ito, Hiromi; Kameyama, Akihiko; Gotoh, Masao; Narimatsu, Hisashi

doi:10.1093/glycob/cwl035

Cited by 74 publications

(57 citation statements)

References 56 publications

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“…The fucosylation motif is highly conserved in the CSVTCGNG sequence in CS αTSR. Fucose can be further modified by addition of β1-3 glucose (33,34). PSI-BLAST searches suggest POFUT2 (and not POFUT1, a homolog involved in Notch fucosylation) is conserved in P. falciparum (gene ID PFI0445c) and other apicomplexans.…”

Section: Discussionmentioning

confidence: 99%

Unexpected fold in the circumsporozoite protein target of malaria vaccines

Doud

Koksal

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

157

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Circumsporozoite (CS) protein is the major surface component of Plasmodium falciparum sporozoites and is essential for host cell invasion. A vaccine containing tandem repeats, region III, and thrombospondin type-I repeat (TSR) of CS is efficacious in phase III trials but gives only a 35% reduction in severe malaria in the first year postimmunization. We solved crystal structures showing that region III and TSR fold into a single unit, an "αTSR" domain. The αTSR domain possesses a hydrophobic pocket and core, missing in TSR domains. CS binds heparin, but αTSR does not. Interestingly, polymorphic T-cell epitopes map to specialized αTSR regions. The N and C termini are unexpectedly close, providing clues for sporozoite sheath organization. Elucidation of a unique structure of a domain within CS enables rational design of next-generation subunit vaccines and functional and medicinal chemical investigation of the conserved hydrophobic pocket.

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Section: Discussionmentioning

confidence: 99%

Unexpected fold in the circumsporozoite protein target of malaria vaccines

Doud

Koksal

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

157

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“…PPS is a rare disease characterized by the association of Peters anomalies, represented by the triad of central corneal opacity, defects in the posterior layers of the cornea and lenticulo-corneal and/or irido-corneal adhesions, with systemic features such as short stature, short broad hands with fifth finger clinodactyly, distinctive facial features, cleft lip and/or cleft palate, hearing loss, abnormal ears, heart defects, genitourinary anomalies, mental retardation and CNS abnormalities [1][2][3].…”

Section: Discussionmentioning

confidence: 99%

Peters Plus Syndrome: Another Way to See a Known Syndrome

Grande¹,

Ciabattoni²,

Andreucci³

et al. 2017

J Genet Syndr Gene Ther

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“…In the meantime, we and others (6,7) found that B3GALTL does not in fact code for a galactosyltransferase but rather for a glucosyltransferase, ␤3Glc-T, that is involved in the synthesis of the unusual disaccharide Glc-␤1,3-Fuc-O-. This small O-linked glycan has been found in the TSRs of thrombospondin-1 (8), properdin, f-spondin (9), ADAMTS-like 1 (10), and ADAMTS-13 (11).…”

mentioning

confidence: 88%

“…Further elongation by ␤4-galactosyltransferase 1 and a sialyltransferase yields the tetrasaccharide NeuAc␣2,6Gal␤1,4GlcNAc␤1,3Fuc-␣1-O- (16,17). It is important to note that the enzymes of the two pathways are specific for either TSRs or epidermal growth factorlike repeats and do not cross-react (6,7,18).…”

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confidence: 99%

Peters Plus Syndrome Is a New Congenital Disorder of Glycosylation and Involves Defective O-Glycosylation of Thrombospondin Type 1 Repeats

Heß

Keusch

Oberstein

et al. 2008

Journal of Biological Chemistry

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Peters Plus syndrome is an autosomal recessive disorder characterized by anterior eye chamber defects, disproportionate short stature, developmental delay, and cleft lip and/or palate. It is caused by splice site mutations in what was thought to be a ␤1,3-galactosyltransferase-like gene (B3GALTL). Recently, we and others found this gene to encode a ␤1,3-glucosyltransferase involved in the synthesis of the disaccharide Glc-␤1,3-Fuc-Othat occurs on thrombospondin type 1 repeats of many biologically important proteins. No functional tests have been performed to date on the presumed glycosylation defect in Peters Plus syndrome. We have established a sensitive immunopurification-mass spectrometry method, using multiple reaction monitoring, to analyze O-fucosyl glycans. It was used to compare the reporter protein properdin from Peters Plus patients with that from control heterozygous relatives. In properdin from patients, we could not detect the Glc-␤1,3-Fuc-O-disaccharide, and we only found Fuc-O-at all four O-fucosylation sites. In contrast, properdin from heterozygous relatives and a healthy volunteer carried the Glc-␤1,3-Fuc-O-disaccharide. These data firmly establish Peters Plus syndrome as a new congenital disorder of glycosylation.Glycosylation is the most common and diverse way by which protein molecules are modified. The biological importance of this co-and post-translational modification is becoming increasingly clear from the rapidly rising number of congenital disorders of glycosylation (CDG) 2 (1, 2). Recently, Lesnik Oberstein et al. (3) discovered that Peters Plus syndrome (MIM 261540) is caused by truncating mutations in a ␤1,3-galactosyltransferase-like gene (B3GALTL) that was originally identified by Heinonen et al. (4). The characteristic features of this disorder include anterior eye chamber defects, disproportionate short stature, developmental delay, and cleft lip and/or palate (5). Peters Plus syndrome was classified as a putative CDG (2), because it is not known whether the mutations affect a specific enzymatic activity or cause the formation of a defective glycan structure.In the meantime, we and others (6, 7) found that B3GALTL does not in fact code for a galactosyltransferase but rather for a glucosyltransferase, ␤3Glc-T, that is involved in the synthesis of the unusual disaccharide Glc-␤1,3-Fuc-O-. This small O-linked glycan has been found in the TSRs of thrombospondin-1 (8), properdin, f-spondin (9), ADAMTS-like 1 (10), and ADAMTS-13 (11). TSRs are independent folding modules of ϳ60 amino acids in length that contain three disulfide bonds and a core consisting of alternating tryptophan and arginine residues. The human genome encodes ϳ100 TSR-containing proteins that perform a variety of important biological functions, including regulation of the coagulation system by proteolysis, inhibition of angiogenesis, and cell and axon guidance (12).The biosynthesis of Glc-␤1,3-Fuc-O-is initiated by the protein O-fucosyltransferase 2 (POFUT2), which attaches the fucosyl residue to a serine or threoni...

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Molecular cloning and characterization of a novel human 1,3-glucosyltransferase, which is localized at the endoplasmic reticulum and glucosylates O-linked fucosylglycan on thrombospondin type 1 repeat domain

Cited by 74 publications

References 56 publications

Unexpected fold in the circumsporozoite protein target of malaria vaccines

Unexpected fold in the circumsporozoite protein target of malaria vaccines

Peters Plus Syndrome: Another Way to See a Known Syndrome

Peters Plus Syndrome Is a New Congenital Disorder of Glycosylation and Involves Defective O-Glycosylation of Thrombospondin Type 1 Repeats

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