Structural basis for DNA recognition by FOXC2

被引：41

作者：

Chen, Xiaojuan ^{[1
,2
,3
,4
]}

Wei, Hudie ^{[1
,2
]}

Li, Jun ^{[1
,2
]}

Liang, Xujun ^{[1
,2
]}

Dai, Shuyan ^{[1
,2
]}

Jiang, Longying ^{[1
,2
]}

Guo, Ming ^{[1
,2
]}

Qu, Lingzhi ^{[1
,2
]}

Chen, Zhuchu ^{[1
,2
]}

Chen, Lin ^{[5
,6
]}

Chen, Yongheng ^{[1
,2
,3
,4
]}

机构：

[1] Cent S Univ, Xiangya Hosp, NHC Key Lab Canc Prote, Changsha 410008, Hunan, Peoples R China

[2] Cent S Univ, Xiangya Hosp, Lab Struct Biol, Changsha 410008, Hunan, Peoples R China

[3] Cent S Univ, Key Lab Med Genet, Changsha 410008, Hunan, Peoples R China

[4] Cent S Univ, Coll Life Sci, Changsha 410008, Hunan, Peoples R China

[5] Univ Southern Calif, Mol & Computat Biol Program, Dept Biol Sci, Los Angeles, CA 90089 USA

[6] Univ Southern Calif, Dept Chem, Los Angeles, CA 90089 USA

来源：

NUCLEIC ACIDS RESEARCH | 2019年 / 47卷 / 07期

基金：

中国国家自然科学基金;

关键词：

FORKHEAD/WINGED-HELIX GENE; TRANSCRIPTION FACTOR; BINDING-SPECIFICITY; CRYSTAL-STRUCTURE; DOMAIN; MECHANISMS; REGULATOR; REVEALS; PROTEIN; MUTATIONS;

D O I：

10.1093/nar/gkz077

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：

The FOXC family of transcription factors (FOXC1 and FOXC2) plays essential roles in the regulation of embryonic, ocular, and cardiac development. Mutations and abnormal expression of FOXC proteins are implicated in genetic diseases as well as cancer. In this study, we determined two crystal structures of the DNA-binding domain (DBD) of human FOXC2 protein, in complex with different DNA sites. The FOXC2-DBD adopts the winged-helix fold with helix H3 contributing to all the base specific contacts, while the N-terminus, wing 1, and the C-terminus of FOXC2-DBD all make additional contacts with the phosphate groups of DNA. Our structural, biochemical, and bioinformatics analyses allow us to revise the previously proposed DNA recognition mechanism and provide a model of DNA binding for the FOXC proteins. In addition, our structural analysis and accompanying biochemical assays provide a molecular basis for understanding disease-causing mutations in FOXC1 and FOXC2.

引用

页码：3752 / 3764

页数：13

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