Structural basis for receptor recognition and pore formation of a zebrafish aerolysin-like protein

被引：53

作者：

Jia, Ning ^{[1
,2
]}

Liu, Nan ^{[3
]}

Cheng, Wang ^{[1
,2
]}

Jiang, Yong-Liang ^{[1
,2
]}

Sun, Hui ^{[1
,2
]}

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

Peng, Junhui ^{[1
,2
]}

Zhang, Yonghui ^{[1
,2
]}

Ding, Yue-He ^{[4
]}

Zhang, Zhi-Hui ^{[1
,2
]}

Wang, Xuejuan ^{[1
,2
]}

Cai, Gang ^{[1
,2
]}

Wang, Junfeng ^{[5
]}

Dong, Meng-Qiu ^{[4
]}

Zhang, Zhiyong ^{[1
,2
]}

Wu, Hui ^{[6
,7
,8
,9
]}

Wang, Hong-Wei ^{[3
]}

Chen, Yuxing ^{[1
,2
]}

Zhou, Cong-Zhao ^{[1
,2
]}

机构：

[1] Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230026, Peoples R China

[2] Univ Sci & Technol China, Sch Life Sci, Hefei 230026, Peoples R China

[3] Tsinghua Univ, Tsinghua Peking Joint Ctr Life Sci, Struct Biol Ctr, Minist Educ,Key Lab Prot Sci,Sch Life Sci, Beijing 100084, Peoples R China

[4] Natl Inst Biol Sci, Beijing, Peoples R China

[5] Chinese Acad Sci, High Field Magnet Lab, Hefei Inst Phys Sci, Hefei, Peoples R China

[6] Univ Alabama Birmingham, Sch Dent, Dept Microbiol, Birmingham, AL 35294 USA

[7] Univ Alabama Birmingham, Sch Dent, Dept Pediat Dent, Birmingham, AL 35294 USA

[8] Univ Alabama Birmingham, Sch Med, Dept Microbiol, Birmingham, AL 35294 USA

[9] Univ Alabama Birmingham, Sch Med, Dept Pediat Dent, Birmingham, AL USA

来源：

EMBO REPORTS | 2016年 / 17卷 / 02期

基金：

中国国家自然科学基金;

关键词：

crystal structure; electron microscopy reconstruction; high-mannose glycan; pore-forming protein; vertebrate; CARBOHYDRATE-BINDING; INACTIVATING PROTEIN; CRYSTAL-STRUCTURE; PLASMA-MEMBRANE; LECTIN REVEALS; CROSS-LINKING; CDNA CLONING; CYANOVIRIN-N; X-RAY; COMPLEX;

D O I：

10.15252/embr.201540851

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Various aerolysin-like pore-forming proteins have been identified from bacteria to vertebrates. However, the mechanism of receptor recognition and/or pore formation of the eukaryotic members remains unknown. Here, we present the first crystal and electron microscopy structures of a vertebrate aerolysin-like protein from Danio rerio, termed Dln1, before and after pore formation. Each subunit of Dln1 dimer comprises a -prism lectin module followed by an aerolysin module. Specific binding of the lectin module toward high-mannose glycans triggers drastic conformational changes of the aerolysin module in a pH-dependent manner, ultimately resulting in the formation of a membrane-bound octameric pore. Structural analyses combined with computational simulations and biochemical assays suggest a pore-forming process with an activation mechanism distinct from the previously characterized bacterial members. Moreover, Dln1 and its homologs are ubiquitously distributed in bony fishes and lamprey, suggesting a novel fish-specific defense molecule.

引用

页码：235 / 248

页数：14

共 65 条

[1] Plasma membrane microdomains act as concentration platforms to facilitate intoxication by aerolysin [J].