Improved secretion of glycoproteins using an N-glycan-restricted passport sequence tag recognized by cargo receptor

被引：17

作者：

Yagi, Hirokazu ^{[1
]}

Yagi-Utsumi, Maho ^{[1
,2
,3
,4
]}

Honda, Rena ^{[1
,3
,4
]}

Ohta, Yusaku ^{[2
,5
]}

Saito, Taiki ^{[1
]}

Nishio, Miho ^{[1
]}

Ninagawa, Satoshi ^{[3
]}

Suzuki, Kousuke ^{[1
]}

Anzai, Takahiro ^{[3
]}

Kamiya, Yukiko ^{[3
]}

Aoki, Kazuhiro ^{[2
,5
]}

Nakanishi, Mahito ^{[6
]}

Satoh, Tadashi ^{[1
]}

Kato, Koichi ^{[1
,2
,3
,4
]}

机构：

[1] Nagoya City Univ, Grad Sch Pharmaceut Sci, Mizuho Ku, 3-1 Tanabe Dori, Nagoya, Aichi 4678603, Japan

[2] Natl Inst Nat Sci, Exploratory Res Ctr Life & Living Syst ExCELLS, 5-1 Higashiyama, Okazaki, Aichi 4448787, Japan

[3] Natl Inst Nat Sci, Inst Mol Sci, 5-1 Higashiyama, Okazaki, Aichi 4448787, Japan

[4] SOKENDAI Grad Univ Adv Studies, Sch Phys Sci, 5-1 Higashiyama, Okazaki, Aichi 4448787, Japan

[5] Natl Inst Nat Sci, Natl Inst Basic Biol, 5-1 Higashiyama, Okazaki, Aichi 4448787, Japan

[6] Natl Inst Adv Ind Sci & Technol, Biotechnol Res Inst Drug Discovery, 1-1-1 Higashi,Cent 5, Tsukuba, Ibaraki 3058565, Japan

来源：

NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期

关键词：

COMBINED DEFICIENCY; FACTOR-VIII; FACTOR-V; ERGIC-53; ANTIBODY; BINDING; COMPARTMENT; MUTATIONS; INSIGHT; LMAN1;

D O I：

10.1038/s41467-020-15192-1

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

MCFD2 and ERGIC-53, which are the products of causative genes of combined factor V and factor VIII deficiency, form a cargo receptor complex responsible for intracellular transport of these coagulation factors in the early secretory pathway. In this study, using an NMR technique, we successfully identified an MCFD2-binding segment from factor VIII composed of a 10 amino acid sequence that enhances its secretion. This prompted us to examine possible effects of attaching this sequence to recombinant glycoproteins on their secretion. We found that the secretion level of recombinant erythropoietin was significantly increased simply by tagging it with the passport sequence. Our findings not only provide molecular basis for the intracellular trafficking of coagulation factors and their genetic deficiency but also offer a potentially useful tool for increasing the production yields of recombinant glycoproteins of biopharmaceutical interest.

引用

页数：9

共 2 条

[1] Improved secretion of glycoproteins using an N-glycan-restricted passport sequence tag recognized by cargo receptor
Hirokazu Yagi
Maho Yagi-Utsumi
Rena Honda
Yusaku Ohta
Taiki Saito
Miho Nishio
Satoshi Ninagawa
Kousuke Suzuki
Takahiro Anzai
Yukiko Kamiya
Kazuhiro Aoki
Mahito Nakanishi
Tadashi Satoh
Koichi Kato
Nature Communications, 11
[2] Molecular tag for promoting N-glycan maturation in the cargo receptor-mediated secretion pathway
Yagi, Hirokazu
Yamada, Rino
Saito, Taiki
Honda, Rena
Nakano, Rio
Inutsuka, Kengo
Tateo, Seigo
Kusano, Hideo
Nishimura, Kumiko
Yanaka, Saeko
Tojima, Takuro
Nakano, Akihiko
Furukawa, Jun-ichi
Yagi-Utsumi, Maho
Adachi, Shungo
Kato, Koichi
ISCIENCE, 2024, 27 (12)

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