The interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferences

被引：40

作者：

de las Rivas, Matilde ^{[1
]}

Lira-Navarrete, Erandi ^{[1
,2
]}

Paul Daniel, Earnest James ^{[3
]}

Companon, Ismael ^{[4
]}

Coelho, Helena ^{[5
,6
,7
]}

Diniz, Ana ^{[5
]}

Jimenez-Barbero, Jesus ^{[6
,7
,8
]}

Peregrina, Jesus M. ^{[4
]}

Clausen, Henrik ^{[2
]}

Corzana, Francisco ^{[4
]}

Marcelo, Filipa ^{[5
]}

Jimenez-Oses, Gonzalo ^{[4
]}

Gerken, Thomas A. ^{[3
,9
,10
]}

Hurtado-Guerrero, Ramon ^{[1
,11
]}

机构：

[1] Univ Zaragoza, BIFI IQFR CSIC Joint Unit, BIFI, Mariano Esquillor S-N,Campus Rio Ebro, Zaragoza 50018, Spain

[2] Univ Copenhagen, Sch Dent, Dept Cellular & Mol Med, Copenhagen Ctr Glyc, DK-2200 Copenhagen, Denmark

[3] Case Western Reserve Univ, Dept Biochem, Cleveland, OH 44106 USA

[4] Univ La Rioja, Dept Quim, Ctr Invest Sintesis Quim, E-26006 Logrono, Spain

[5] Univ Nova Lisboa, Fac Ciencias & Tecnol, Dept Quim, UCIBIO,REQUIMTE, P-2829516 Caparica, Portugal

[6] CIC bioGUNE, Bizkaia Technol Pk,Bldg 801A, Derio 48170, Spain

[7] Univ Basque Country, Fac Sci & Technol, Dept Organ Chem 2, Leioa 48940, Bizkaia, Spain

[8] Basque Fdn Sci, Ikerbasque, Maria Diaz de Haro 13, Bilbao 48009, Spain

[9] Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA

[10] Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA

[11] Fdn ARAID, Zaragoza 50018, Spain

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

美国国家卫生研究院; 新加坡国家研究基金会;

关键词：

O-GLYCOSYLATION; N-ACETYLGALACTOSAMINYLTRANSFERASE; LECTIN DOMAINS; UDP-GALNAC; CCP4; SUITE; BINDING; RECOGNITION;

D O I：

10.1038/s41467-017-02006-0

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：

The polypeptide GalNAc-transferases (GalNAc-Ts), that initiate mucin-type O-glycosylation, consist of a catalytic and a lectin domain connected by a flexible linker. In addition to recognizing polypeptide sequence, the GalNAc-Ts exhibit unique long-range N-and/or Cterminal prior glycosylation (GalNAc-O-Ser/Thr) preferences modulated by the lectin domain. Here we report studies on GalNAc-T4 that reveal the origins of its unique N-terminal long-range glycopeptide specificity, which is the opposite of GalNAc-T2. The GalNAc-T4 structure bound to a monoglycopeptide shows that the GalNAc-binding site of its lectin domain is rotated relative to the homologous GalNAc-T2 structure, explaining their different long-range preferences. Kinetics and molecular dynamics simulations on several GalNAc-T2 flexible linker constructs show altered remote prior glycosylation preferences, confirming that the flexible linker dictates the rotation of the lectin domain, thus modulating the GalNAc-Ts' long-range preferences. This work for the first time provides the structural basis for the different remote prior glycosylation preferences of the GalNAc-Ts.

引用

页数：11

共 37 条

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