DNA recognition by the RUNX1 transcription factor is mediated by an allosteric transition in the Runt domain and by DNA bending

被引：49

作者：

Bartfeld, D

Shimon, L

Couture, GC

Rabinovich, D

Frolow, F

Levanon, D

Groner, Y

Shakked, Z ^{[1
]}

机构：

[1] Weizmann Inst Sci, Dept Biol Struct, IL-76100 Rehovot, Israel

[2] Weizmann Inst Sci, Chem Serv, IL-76100 Rehovot, Israel

[3] Tel Aviv Univ, Dept Biotechnol & Microbiol, IL-69978 Tel Aviv, Israel

[4] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel

来源：

STRUCTURE | 2002年 / 10卷 / 10期

基金：

以色列科学基金会;

关键词：

allosteric transition; crystal structure; DNA conformation; gene regulation; RUNX1 Runt domain;

D O I：

10.1016/S0969-2126(02)00853-5

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

The Runt domain proteins are transcription regulators of major developmental pathways. Here we present the crystal structures of the Runt domain (RD) of the human protein RUNX1 and its DNA binding site in their free states and compare them with the published crystal structures of RD bound to DNA and to the partner protein CBFbeta. We demonstrate that (1) RD undergoes an allosteric transition upon DNA binding, which is further stabilized by CBFbeta, and that (2) the free DNA target adopts a bent-helical conformation compatible with that of the complex. These findings elucidate the mechanism by which CBFbeta enhances RD binding to DNA as well as the role of the intrinsic conformation of the DNA target in the recognition process.

引用

页码：1395 / 1407

页数：13

共 60 条

[1]

A simple screening for mutant DNA binding proteins: Application to murine transcription factor PEBP2 alpha subunit, a founding member of the Runt domain protein family [J].