Imperfect interface of Beclin1 coiled-coil domain regulates homodimer and heterodimer formation with Atg14L and UVRAG

被引：141

作者：

Li, Xiaohua ^{[1
]}

He, Liqiang ^{[2
]}

Che, Ka Hing ^{[1
]}

Funderburk, Sarah F. ^{[2
]}

Pan, Lifeng ^{[3
]}

Pan, Nina ^{[2
]}

Zhang, Mingjie ^{[3
]}

Yue, Zhenyu ^{[2
]}

Zhao, Yanxiang ^{[1
]}

机构：

[1] Hong Kong Polytech Univ, State Key Lab Chirosci, Dept Appl Biol & Chem Technol, Kowloon, Hong Kong, Peoples R China

[2] Mt Sinai Sch Med, Friedman Brain Inst, Dept Neurol & Neurosci, New York, NY 10029 USA

[3] Hong Kong Univ Sci & Technol, Div Life Sci, State Key Lab Mol Neurosci, Kowloon, Hong Kong, Peoples R China

来源：

NATURE COMMUNICATIONS | 2012年 / 3卷

关键词：

TUMOR-SUPPRESSOR; PHOSPHATIDYLINOSITOL; 3-KINASE; MOLECULAR-GRAPHICS; SELF-DIGESTION; AUTOPHAGY GENE; COMPLEX; PROTEIN; TUMORIGENESIS; TRAFFICKING; ASSOCIATION;

D O I：

10.1038/ncomms1648

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：

Beclin 1 is a core component of the Class III Phosphatidylinositol 3-Kinase VPS34 complex. The coiled coil domain of Beclin 1 serves as an interaction platform for assembly of distinct Atg14L- and UVRAG-containing complexes to modulate VPS34 activity. Here we report the crystal structure of the coiled coil domain that forms an antiparallel dimer and is rendered metastable by a series of 'imperfect' a-d' pairings at its coiled coil interface. Atg14L and UVRAG promote the transition of metastable homodimeric Beclin 1 to heterodimeric Beclin1-Atg14L/UVRAG assembly. Beclin 1 mutants with their 'imperfect' a-d' pairings modified to enhance self-interaction, show distinctively altered interactions with Atg14L or UVRAG. These results suggest that specific utilization of the dimer interface and modulation of the homodimer heterodimer transition by Beclin 1-interacting partners may underlie the molecular mechanism that controls the formation of various Beclin1-VPS34 subcomplexes to exert their effect on an array of VPS34-related activities, including autophagy.

引用

页数：11

共 41 条

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