Initiation of O-glycan synthesis in IgA1 hinge region is determined by a single enzyme, UDP-N-acetyl-α-D-galactosamine:: Polypeptide N-acetylgalactosaminyltransferase 2

被引:80
作者
Iwasaki, H
Zhang, Y
Tachibana, K
Gotoh, M
Kikuchi, N
Kwon, YD
Togayachi, A
Kudo, T
Kubota, T
Narimatsu, H
机构
[1] Natl Inst Adv Ind Sci & Technol, AIST, Res Ctr Glycosci, Open Space Lab,Glycogene Funct Team, Tsukuba, Ibaraki 3058568, Japan
[2] Amersham Biosci KK, Shinjuku Ku, Tokyo, Japan
[3] Mitsui Knowledge Ind Co Ltd, Nakano Ku, Tokyo 1648721, Japan
[4] New Energy & Ind Technol Dev Org, Toshima Ku, Tokyo 1706028, Japan
关键词
D O I
10.1074/jbc.M211097200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The hinge region of human immunoglobulin A1 (*IgA1) possesses multiple O-glycans, of which synthesis is initiated by the addition of GaINAc to serine or threonine through the activity of UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferases (pp-GaINAc-Ts). We found that six pp-GaINAc-Ts, ppGaINAc-T1, -T2, -T3, -T4, -T6, and -T9, were expressed in B cells, IgA-bearing B cells, and NCI-H929 IgA myeloma cells. pp-GaINAc-T activities of these six enzymes for a synthetic IgA hinge peptide, which has nine possible O-glycosylation sites, were examined using a reversed phase-high performance liquid chromatography, a matrix-assisted laser desorption ionization time of flight mass spectrometry, and peptide sequencing analysis. pp-GaINAc-T2 showed the strongest activity transferring GaINAe to a maximum of eight positions. Other pp-GaINAc-Ts exhibited different substrate specificities from pp-GaINAc-T2; however, their activities were extremely weak. It was reported that the IgA1 hinge region possesses a maximum of five O-glycans, and their amino acid positions have been determined. We found that pp-GaINAc-T2 selectively transferred GaINAc residues to the same five positions. These results strongly suggested that pp-GaINAc-T2 is an essential enzyme for initiation of O-linked glycosylation of the IgA1 hinge region.
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页码:5613 / 5621
页数:9
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