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可变亚基界面强度对血红蛋白表达的内在调节。

Intrinsic regulation of hemoglobin expression by variable subunit interface strengths.

机构信息

Department of Biology, Northeastern University, Boston, MA 02115, USA.

出版信息

FEBS J. 2012 Feb;279(3):361-9. doi: 10.1111/j.1742-4658.2011.08437.x. Epub 2011 Dec 22.

DOI:10.1111/j.1742-4658.2011.08437.x
PMID:22129306
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3270300/
Abstract

The expression of the six types of human Hb subunits over time is currently considered to be regulated mainly by transcription factors that bind to upstream control regions of the gene (the 'extrinsic' component of regulation). Here, we describe how subunit pairing and further assembly to tetramers in the liganded state is influenced by the affinity of subunits for one another (the 'intrinsic' component of regulation). The adult Hb dimers have the strongest subunit interfaces and the embryonic Hbs the weakest, with fetal Hbs being of intermediate strength, corresponding to the temporal order of their expression. These variable subunit binding strengths and the attenuating effects of acetylation contribute to the differences with which these Hb types form functional O(2) -binding tetramers consistent with gene switching.

摘要

目前,人们认为人类 Hb 亚基的六种类型随时间的表达主要受到与基因上游控制区结合的转录因子的调节(调节的“外在”成分)。在这里,我们描述了亚基之间的配对以及在配体结合状态下进一步组装成四聚体如何受到亚基彼此亲和力的影响(调节的“内在”成分)。成人 Hb 二聚体具有最强的亚基界面,而胚胎 Hbs 则最弱,胎儿 Hbs 处于中间强度,与它们表达的时间顺序相对应。这些可变的亚基结合强度和乙酰化的衰减作用导致这些 Hb 类型形成与基因转换一致的功能性 O(2)结合四聚体的能力存在差异。

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本文引用的文献

1
Developmental expression of human hemoglobins mediated by maturation of their subunit interfaces.通过亚基界面成熟介导的人类血红蛋白的发育表达。
Protein Sci. 2010 Aug;19(8):1595-9. doi: 10.1002/pro.441.
2
Energetic differences at the subunit interfaces of normal human hemoglobins correlate with their developmental profile.正常人血红蛋白亚基界面处的能量差异与其发育特征相关。
Biochemistry. 2009 Aug 18;48(32):7568-74. doi: 10.1021/bi900857r.
3
Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A.人类胎儿血红蛋白的表达受发育阶段特异性阻遏物BCL11A调控。
Science. 2008 Dec 19;322(5909):1839-42. doi: 10.1126/science.1165409. Epub 2008 Dec 4.
4
Human embryonic, fetal, and adult hemoglobins have different subunit interface strengths. Correlation with lifespan in the red cell.人类胚胎、胎儿和成人血红蛋白具有不同的亚基界面强度。与红细胞寿命的相关性。
Protein Sci. 2007 Aug;16(8):1641-58. doi: 10.1110/ps.072891007.
5
Understanding alpha-globin gene regulation: Aiming to improve the management of thalassemia.了解α-珠蛋白基因调控:旨在改善地中海贫血的管理。
Ann N Y Acad Sci. 2005;1054:92-102. doi: 10.1196/annals.1345.012.
6
GATA1 function, a paradigm for transcription factors in hematopoiesis.GATA1功能,造血过程中转录因子的一个范例。
Mol Cell Biol. 2005 Feb;25(4):1215-27. doi: 10.1128/MCB.25.4.1215-1227.2005.
7
Measuring assembly and binding in human embryonic hemoglobins.测量人类胚胎血红蛋白中的组装和结合。
Methods Enzymol. 2004;379:64-80. doi: 10.1016/S0076-6879(04)79004-7.
8
HUMAN HAEMOGLOBINS.人类血红蛋白
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