Bisecting GlcNAc Is a General Suppressor of Terminal Modification of N-glycan

Miyako Nakano, Sushil K. Mishra, Yuko Tokoro, Keiko Sato, Kazuki Nakajima, Yoshiki Yamaguchi, Naoyuki Taniguchi, Yasuhiko Kizuka

研究成果: Article

抄録

Glycoproteins are decorated with complex glycans for protein functions. However, regulation mechanisms of complex glycan biosynthesis are largely unclear. Here we found that bisecting GlcNAc, a branching sugar residue in N-glycan, suppresses the biosynthesis of various types of terminal epitopes in N-glycans, including fucose, sialic acid and human natural killer-1. Expression of these epitopes in N-glycan was elevated in mice lacking the biosynthetic enzyme of bisecting GlcNAc, GnT-III, and was conversely suppressed by GnT-III overexpression in cells. Many glycosyltransferases for N-glycan terminals were revealed to prefer a nonbisected N-glycan as a substrate to its bisected counterpart, whereas no up-regulation of their mRNAs was found. This indicates that the elevated expression of the terminal N-glycan epitopes in GnT-III-deficient mice is attributed to the substrate specificity of the biosynthetic enzymes. Molecular dynamics simulations further confirmed that nonbisected glycans were preferentially accepted by those glycosyltransferases. These findings unveil a new regulation mechanism of protein N-glycosylation.

元の言語English
ページ(範囲)2044-2057
ページ数14
ジャーナルMolecular & cellular proteomics : MCP
18
発行部数10
DOI
出版物ステータスPublished - 01-10-2019

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Polysaccharides
Epitopes
Biosynthesis
Glycosylation
Glycosyltransferases
Fucose
N-Acetylneuraminic Acid
Substrates
Enzymes
Molecular Dynamics Simulation
Substrate Specificity
Sugars
Molecular dynamics
Glycoproteins
Proteins
Up-Regulation
Messenger RNA
Computer simulation

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Biochemistry
  • Molecular Biology

これを引用

Nakano, Miyako ; Mishra, Sushil K. ; Tokoro, Yuko ; Sato, Keiko ; Nakajima, Kazuki ; Yamaguchi, Yoshiki ; Taniguchi, Naoyuki ; Kizuka, Yasuhiko. / Bisecting GlcNAc Is a General Suppressor of Terminal Modification of N-glycan. :: Molecular & cellular proteomics : MCP. 2019 ; 巻 18, 番号 10. pp. 2044-2057.
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abstract = "Glycoproteins are decorated with complex glycans for protein functions. However, regulation mechanisms of complex glycan biosynthesis are largely unclear. Here we found that bisecting GlcNAc, a branching sugar residue in N-glycan, suppresses the biosynthesis of various types of terminal epitopes in N-glycans, including fucose, sialic acid and human natural killer-1. Expression of these epitopes in N-glycan was elevated in mice lacking the biosynthetic enzyme of bisecting GlcNAc, GnT-III, and was conversely suppressed by GnT-III overexpression in cells. Many glycosyltransferases for N-glycan terminals were revealed to prefer a nonbisected N-glycan as a substrate to its bisected counterpart, whereas no up-regulation of their mRNAs was found. This indicates that the elevated expression of the terminal N-glycan epitopes in GnT-III-deficient mice is attributed to the substrate specificity of the biosynthetic enzymes. Molecular dynamics simulations further confirmed that nonbisected glycans were preferentially accepted by those glycosyltransferases. These findings unveil a new regulation mechanism of protein N-glycosylation.",
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Nakano, M, Mishra, SK, Tokoro, Y, Sato, K, Nakajima, K, Yamaguchi, Y, Taniguchi, N & Kizuka, Y 2019, 'Bisecting GlcNAc Is a General Suppressor of Terminal Modification of N-glycan', Molecular & cellular proteomics : MCP, 巻. 18, 番号 10, pp. 2044-2057. https://doi.org/10.1074/mcp.RA119.001534

Bisecting GlcNAc Is a General Suppressor of Terminal Modification of N-glycan. / Nakano, Miyako; Mishra, Sushil K.; Tokoro, Yuko; Sato, Keiko; Nakajima, Kazuki; Yamaguchi, Yoshiki; Taniguchi, Naoyuki; Kizuka, Yasuhiko.

:: Molecular & cellular proteomics : MCP, 巻 18, 番号 10, 01.10.2019, p. 2044-2057.

研究成果: Article

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T1 - Bisecting GlcNAc Is a General Suppressor of Terminal Modification of N-glycan

AU - Nakano, Miyako

AU - Mishra, Sushil K.

AU - Tokoro, Yuko

AU - Sato, Keiko

AU - Nakajima, Kazuki

AU - Yamaguchi, Yoshiki

AU - Taniguchi, Naoyuki

AU - Kizuka, Yasuhiko

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Glycoproteins are decorated with complex glycans for protein functions. However, regulation mechanisms of complex glycan biosynthesis are largely unclear. Here we found that bisecting GlcNAc, a branching sugar residue in N-glycan, suppresses the biosynthesis of various types of terminal epitopes in N-glycans, including fucose, sialic acid and human natural killer-1. Expression of these epitopes in N-glycan was elevated in mice lacking the biosynthetic enzyme of bisecting GlcNAc, GnT-III, and was conversely suppressed by GnT-III overexpression in cells. Many glycosyltransferases for N-glycan terminals were revealed to prefer a nonbisected N-glycan as a substrate to its bisected counterpart, whereas no up-regulation of their mRNAs was found. This indicates that the elevated expression of the terminal N-glycan epitopes in GnT-III-deficient mice is attributed to the substrate specificity of the biosynthetic enzymes. Molecular dynamics simulations further confirmed that nonbisected glycans were preferentially accepted by those glycosyltransferases. These findings unveil a new regulation mechanism of protein N-glycosylation.

AB - Glycoproteins are decorated with complex glycans for protein functions. However, regulation mechanisms of complex glycan biosynthesis are largely unclear. Here we found that bisecting GlcNAc, a branching sugar residue in N-glycan, suppresses the biosynthesis of various types of terminal epitopes in N-glycans, including fucose, sialic acid and human natural killer-1. Expression of these epitopes in N-glycan was elevated in mice lacking the biosynthetic enzyme of bisecting GlcNAc, GnT-III, and was conversely suppressed by GnT-III overexpression in cells. Many glycosyltransferases for N-glycan terminals were revealed to prefer a nonbisected N-glycan as a substrate to its bisected counterpart, whereas no up-regulation of their mRNAs was found. This indicates that the elevated expression of the terminal N-glycan epitopes in GnT-III-deficient mice is attributed to the substrate specificity of the biosynthetic enzymes. Molecular dynamics simulations further confirmed that nonbisected glycans were preferentially accepted by those glycosyltransferases. These findings unveil a new regulation mechanism of protein N-glycosylation.

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