Diabetes-associated mutations in a p-cell transcription factor destabilize an antiparallel 'mini-zipper' in a dimerization interface

Qing-Xin Hua; Ming Zhaot; Narendra Narayana

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Diabetes-associated mutations in a p-cell transcription factor destabilize an antiparallel 'mini-zipper' in a dimerization interface

机译：p细胞转录因子中与糖尿病相关的突变使二聚化界面中的反平行“迷你拉链”不稳定

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摘要

Maturity-onset diabetes of the young, a monogenic form of Type Il diabetes mellitus, is most commonly caused by mutation in hepatic nuclear factor 1α(HNF-1α). Here, the dimerization motif of HNF-1α is shown to form an intermolecular four-helix bundle. One face contains an antiparallel coiled coil whereas the other contains splayed a-helices. The "mini-zipper" is complementary in structure and symmetry to the top surface of a transcriptional coactivator (dimerization co factor of homeodomains). The bundle is destabi- lized by a subset of mutations associated with maturity-onset diabetes of the young. Impaired dimerization of a p-cell transcrip- tion factor thus provides a molecular mechanism of metabolic deregulation in diabetes mellitus.

机译：II型糖尿病的单基因形式，年轻的成熟期糖尿病最常见是由肝核因子1α（HNF-1α）突变引起的。在此，HNF-1α的二聚化基序显示为形成分子间的四螺旋束。一个面包含反平行的盘绕线圈，而另一个面包含张开的a螺旋。 “迷你拉链”在结构和对称性上与转录共激活因子（同源域的二聚化辅助因子）的顶表面互补。该束被与年轻人成熟发作的糖尿病相关的一部分突变所破坏。 P细胞转录因子的二聚化受损因此提供了糖尿病代谢异常调节的分子机制。

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《Proceedings of the National Academy of Sciences of the United States of America》 |2000年第5期|p.1999-2004|共6页
作者
Qing-Xin Hua; Ming Zhaot; Narendra Narayana;
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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种 eng
中图分类自然科学总论;
关键词
diabetes mellitus; gene regulation; protein structure; NMR;

机译：糖尿病基因调控;蛋白质结构;核磁共振;

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1. Brief Genetics Report: β-Cell Transcription Factors and Diabetes No Evidence for Diabetes-Associated Mutations in the Gene Encoding the Basic Helix-Loop-helix trnascription Factor Neurogenic Differentiation 4 (NEUROD4)in Japanese Patients With MODY [J] . Yohko Horikawa, Yukio Horikawa, Nancy J. Cox Diabetes . 2000,第11期

机译：简要的遗传学报告：在日本MODY患者中，基本的螺旋-螺旋-螺旋转录因子神经原性分化4（NEUROD4）编码基因的β细胞转录因子和糖尿病没有证据表明与糖尿病相关。
2. Hemophilia A Mutations within the Factor VIII A2-A3 Subunit Interface Destabilize Factor VIIIa and Cause One-stage/Two-stage Activity Discrepancy. [J] . Hakeos WH, Miao H, Sirachainan N, Thrombosis and Haemostasis: Journal of the International Society on Thrombosis and Haemostasis . 2002,第5期

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机译：GTF2E2突变使具有DNA修复能力的毛发硫代营养不良症患者的一般转录因子复合物TFIIE不稳定。
4. Homology modeling of the DNA binding and dimerization partner domains of E2F1 transcription factor protein in homo sapiens [C] . Nayan Mohd Yasser, Jusoh Siti Azma, Mutalip Siti Syairah Mohd, 2012 IEEE Symposium on Business, Engineering and Industrial Applications. . 2012

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5. A mutational and functional analysis of C-terminal sequences of human transcription factor REL: Their role in cellular transformation and transcriptional activation. [D] . Starczynowski, Daniel T. 2006

机译：人类转录因子REL C末端序列的突变和功能分析：它们在细胞转化和转录激活中的作用。
6. Diabetes-associated mutations in a β-cell transcription factor destabilize an antiparallel mini-zipper in a dimerization interface [O] . Qing-Xin Hua, Ming Zhao, Narendra Narayana, 2000

机译：β细胞转录因子中与糖尿病相关的突变使二聚化界面中的反平行迷你拉链不稳定
7. Diabetes-associated mutations in a beta -cell transcription factor destabilize an antiparallel "mini-zipper" in a dimerization interface [O] . Q.-X. Hua, M. Zhao, N. Narayana, 2000

机译：β-细胞转录因子中的糖尿病相关突变在二聚化界面中稳定反平行“迷你拉链”

Diabetes-associated mutations in a p-cell transcription factor destabilize an antiparallel 'mini-zipper' in a dimerization interface

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