Interferon-Inducible Protein 16: Insight into the Interaction with Tumor Suppressor p53

被引：82

作者：

Liao, Jack C. C. ^{[1
,2
]}

Lam, Robert ^{[1
,3
]}

Brazda, Vaclav ^{[4
]}

Duan, Shili ^{[1
,2
]}

Ravichandran, Mani ^{[3
]}

Ma, Justin ^{[1
,2
]}

Xiao, Ting ^{[3
]}

Tempel, Wolfram ^{[3
]}

Zuo, Xiaobing ^{[5
]}

Wang, Yun-Xing ^{[5
]}

Chirgadze, Nickolay Y. ^{[1
,6
]}

Arrowsmith, Cheryl H. ^{[1
,2
,3
]}

机构：

[1] Univ Hlth Network, Ontario Canc Inst, Campbell Family Canc Res Inst, Toronto, ON M5G 2C4, Canada

[2] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, Canada

[3] Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L5, Canada

[4] Acad Sci Czech Republic, Inst Biophys, Vvi, CS-61265 Brno, Czech Republic

[5] Natl Canc Inst Frederick, Prot Nucle Acid Interact Sect, Struct Biophys Lab, NIH, Frederick, MD 21702 USA

[6] Univ Toronto, Dept Pharmacol & Toxicol, Toronto, ON M5S 1A8, Canada

来源：

STRUCTURE | 2011年 / 19卷 / 03期

基金：

英国惠康基金;

关键词：

STRANDED-DNA-BINDING; C-TERMINAL DOMAIN; CELLULAR SENESCENCE; NEGATIVE REGULATOR; SSDNA RECOGNITION; CYTOPLASMIC DNA; OB-FOLD; SEQUENCE; FAMILY; ACTIVATION;

D O I：

10.1016/j.str.2010.12.015

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：

IFI16 is a member of the interferon-inducible HIN-200 family of nuclear proteins. It has been implicated in transcriptional regulation by modulating protein-protein interactions with p53 tumor suppressor protein and other transcription factors. However, the mechanisms of interaction remain unknown. Here, we report the crystal structures of both HIN-A and HIN-B domains of IFI16 determined at 2.0 and 2.35 angstrom resolution, respectively. Each HIN domain comprises a pair of tightly packed OB-fold subdomains that appear to act as a single unit. We show that both HIN domains of IFI16 are capable of enhancing p53-DNA complex formation and transcriptional activation via distinctive means. HIN-A domain binds to the basic C terminus of p53, whereas the HIN-B domain binds to the core DNA-binding region of p53. Both interactions are compatible with the DNA-bound state of p53 and together contribute to the effect of full-length IFI16 on p53-DNA complex formation and transcriptional activation.

引用

页码：418 / 429

页数：12

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