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.
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页数：9
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