Structure of a fungal 1,3-β-glucan synthase

被引：11

作者：

Zhao, Chao-Ran ^{[1
,6
,7
]}

You, Zi-Long ^{[1
]}

Chen, Dan-Dan ^{[1
,2
]}

Hang, Jing ^{[2
,3
,4
,5
]}

Wang, Zhao-Bin ^{[1
]}

Ji, Meng ^{[1
]}

Wang, Le-Xuan ^{[1
]}

Zhao, Peng ^{[1
]}

Qiao, Jie ^{[2
,3
,4
,5
]}

Yun, Cai-Hong ^{[1
]}

Bai, Lin ^{[1
]}

机构：

[1] Peking Univ, Sch Basic Med Sci, Dept Biochem & Biophys, Beijing, Peoples R China

[2] Peking Univ Third Hosp, Dept Obstet & Gynecol, Ctr Reprod Med, State Key Lab Female Fertil Promot, Beijing, Peoples R China

[3] Peking Univ Third Hosp, Natl Clin Res Ctr Obstet & Gynecol, Beijing, Peoples R China

[4] Peking Univ Third Hosp, Key Lab Assisted Reprod, Minist Educ, Beijing, Peoples R China

[5] Beijing Key Lab Reprod Endocrinol & Assisted Repr, Beijing, Peoples R China

[6] Capital Med Univ, Beijing Tongren Hosp, Dept Otolaryngol Head & Neck Surg, Beijing 100730, Peoples R China

[7] Beijing Inst Otolaryngol, Beijing Key Lab Nasal Dis, Beijing 100005, Peoples R China

来源：

SCIENCE ADVANCES | 2023年 / 9卷 / 37期

基金：

中国国家自然科学基金; 国家重点研发计划;

关键词：

CELL-WALL; PROTEIN; SUBUNIT; BIOSYNTHESIS; REQUIRES; GTPASE; RHO1P;

D O I：

10.1126/sciadv.adh7820

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：

1,3-beta-Glucan serves as the primary component of the fungal cell wall and is produced by 1,3-beta-glucan synthase located in the plasma membrane. This synthase is a molecular target for antifungal drugs such as echinocandins and the triterpenoid ibrexafungerp. In this study, we present the cryo-electron microscopy structure of Saccharomyces cerevisiae 1,3-beta-glucan synthase (Fks1) at 2.47-A resolution. The structure reveals a central catalytic region adopting a cellulose synthase fold with a cytosolic conserved GT-A-type glycosyltransferase domain and a closed transmembrane channel responsible for glucan transportation. Two extracellular disulfide bonds are found to be crucial for Fks1 enzymatic activity. Through structural comparative analysis with cellulose synthases and structure-guided mutagenesis studies, we gain previously unknown insights into the molecular mechanisms of fungal 1,3-beta-glucan synthase.

引用

页数：9

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