A critical role for the loop region of the basic helix-loop-helix/leucine zipper protein Mlx in DNA binding and glucose-regulated transcription.
A critical role for the loop region of the basic helix-loop-helix/leucine zipper protein Mlx in DNA binding and glucose-regulated transcription.
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DOI：
10.1093/nar/gkl987
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发表时间：
2007
影响因子：
14.9
通讯作者：
Towle HC
中科院分区：
文献类型：
--
作者：
Ma L;Sham YY;Walters KJ;Towle HC
碳水化合物反应元件（ChoRE）是在葡萄糖诱导转录的基因的启动子中发现的顺式作用序列。ChoRE由两个E盒样基序组成，这两个基序相隔5 bp，并被两个碱性螺旋-环-螺旋/亮氨酸拉链（bHLH/LZ）蛋白ChREBP和Mlx识别，它们异源二聚化以结合DNA。在这项研究中，我们证明了两个ChREBP/Mlx异二聚体相互作用，以稳定结合到ChoRE中的串联E盒样基序。基于我们生成的ChREBP/Mlx结合到ChoRE的模型结构，我们假设相邻异源二聚体的Mlx环区域内的残基之间的分子间相互作用负责稳定复合物。我们通过制备Mlx变体来测试这一假设，在Mlx变体中，环区被另一个家族成员的环区替换或在几个关键残基处突变。这些Mlx变体保留了它们与ChREBP作为异二聚体结合到单个完美E盒基序的能力，但不再与ChoRE结合，也不支持葡萄糖响应活性。总之，我们的研究结果支持一个模型，其中Mlx的环区域在介导ChREBP/Mlx异二聚体与ChoRE的配位结合中发挥重要的功能作用。
The carbohydrate response element (ChoRE) is a cis-acting sequence found in the promoters of genes induced transcriptionally by glucose. The ChoRE is composed of two E box-like motifs that are separated by 5 bp and is recognized by two basic helix–loop–helix/leucine zipper (bHLH/LZ) proteins, ChREBP and Mlx, which heterodimerize to bind DNA. In this study, we demonstrate that two ChREBP/Mlx heterodimers interact to stabilize binding to the tandem E box-like motifs in the ChoRE. Based on a model structure that we generated of ChREBP/Mlx bound to the ChoRE, we hypothesized that intermolecular interactions between residues within the Mlx loop regions of adjacent heterodimers are responsible for stabilizing the complex. We tested this hypothesis by preparing Mlx variants in which the loop region was replaced with that of another family member or mutated at several key residues. These Mlx variants retained their ability to bind to a single perfect E-box motif as a heterodimer with ChREBP, but no longer bound to the ChoRE nor supported glucose responsive activity. In summary, our results support a model in which the loop regions of Mlx play an important functional role in mediating the coordinate binding of ChREBP/Mlx heterodimers to the ChoRE.
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影响因子：
4.8
作者：
Ma, L;Tsatsos, NG;Towle, HC
通讯作者：
Towle, HC
DOI：
10.1073/pnas.0401516101
发表时间：
2004-05-11
影响因子：
11.1
作者：
Iizuka, K;Bruick, RK;Uyeda, K
通讯作者：
Uyeda, K
影响因子：
4.8
作者：
Kaytor, EN;Shih, HM;Towle, HC
通讯作者：
Towle, HC
DOI：
10.1006/bbrc.1999.1034
发表时间：
1999-08-02
影响因子：
3.1
作者：
Rufo, C;Gasperikova, D;Nakamura, MT
通讯作者：
Nakamura, MT
影响因子：
4.8
作者：
SHIH, HM;LIU, ZR;TOWLE, HC
通讯作者：
TOWLE, HC