Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1α

被引：395

作者：

Freedman, SJ

Sun, ZYJ

Poy, F

Kung, AL

Livingston, DM

Wagner, G

Eck, MJ

机构：

[1] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

[2] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA

[3] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2002年 / 99卷 / 08期

关键词：

D O I：

10.1073/pnas.082117899

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：

Adaptation to hypoxia is mediated by transactivation of hypoxia-responsive genes by hypoxia-inducible factor-1 (HIF-1) in complex with the CBP and p300 transcriptional coactivators. We report the solution structure of the cysteine/histidine-rich 1 (CH1) domain of p300 bound to the C-terminal transactivation domain of HIF-1alpha. CH1 has a triangular geometry composed of four a-helices with three intervening Zn2+-coordinating centers. CH1 serves as a scaffold for folding of the HIF-1alpha C-terminal transactivation domain, which forms a vise-like clamp on the CH1 domain that is stabilized by extensive hydrophobic and polar interactions. The structure reveals the mechanism of specific recognition of p300 by HIF-1alpha, and shows how HIF-1alpha transactivation is regulated by asparagine hydroxylation.

引用

页码：5367 / 5372

页数：6