我们能从一种小型调节性膜蛋白中学到什么？
What can we learn from a small regulatory membrane protein?
作者信息
Veglia Gianluigi, Ha Kim N, Shi Lei, Verardi Raffaello, Traaseth Nathaniel J
机构信息
Department of Chemistry, University of Minnesota, Minneapolis, MN, USA.
出版信息
Methods Mol Biol. 2010;654:303-19. doi: 10.1007/978-1-60761-762-4_16.
Abstract
This chapter reviews the molecular biology, biochemical, and NMR methods that we used to study the structural dynamics, membrane topology, and interaction of phospholamban (PLN), a small regulatory membrane protein involved in the regulation of the sarcoplasmic reticulum Ca-ATPase (SERCA). In particular, we show the progression of our research from the initial hypotheses toward understanding the molecular mechanisms of SERCA's regulation, including the effects of PLN oligomerization and posttranslational phosphorylation. Finally, we show how the knowledge of the molecular mechanism of the structural dynamics and topology of free and bound proteins can lead to the rational design of PLN analogs for possible use in gene therapy.
摘要
本章回顾了我们用于研究受磷蛋白（PLN）的结构动力学、膜拓扑结构及其相互作用的分子生物学、生物化学和核磁共振方法。PLN是一种参与肌浆网Ca-ATP酶（SERCA）调节的小型调节性膜蛋白。特别是，我们展示了我们的研究从最初的假设到理解SERCA调节分子机制的进展，包括PLN寡聚化和翻译后磷酸化的影响。最后，我们展示了自由和结合蛋白的结构动力学和拓扑分子机制的知识如何能够合理设计PLN类似物，以便可能用于基因治疗。
相似文献
1
What can we learn from a small regulatory membrane protein?我们能从一种小型调节性膜蛋白中学到什么？
Methods Mol Biol. 2010;654:303-19. doi: 10.1007/978-1-60761-762-4_16.
2
Allosteric regulation of SERCA by phosphorylation-mediated conformational shift of phospholamban.通过肌球蛋白结合蛋白 C 的磷酸化介导的构象变化对 SERCA 的变构调节。
Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17338-43. doi: 10.1073/pnas.1303006110. Epub 2013 Oct 7.
3
Activating and deactivating roles of lipid bilayers on the Ca(2+)-ATPase/phospholamban complex.脂质双层在 Ca(2+)-ATP 酶/磷酸化酶抑制蛋白复合物上的激活和失活作用。
Biochemistry. 2011 Nov 29;50(47):10367-74. doi: 10.1021/bi200759y. Epub 2011 Nov 8.
4
Pathological mutations in the phospholamban cytoplasmic region affect its topology and dynamics modulating the extent of SERCA inhibition.细胞质区的磷蛋白结构域病理性突变会影响其拓扑结构和动力学，从而调节 SERCA 抑制的程度。
Biochim Biophys Acta Biomembr. 2024 Oct;1866(7):184370. doi: 10.1016/j.bbamem.2024.184370. Epub 2024 Jul 8.
5
Controlling the inhibition of the sarcoplasmic Ca2+-ATPase by tuning phospholamban structural dynamics.通过调节受磷蛋白的结构动力学来控制肌浆网Ca2 + -ATP酶的抑制作用。
J Biol Chem. 2007 Dec 21;282(51):37205-14. doi: 10.1074/jbc.M704056200. Epub 2007 Sep 30.
6
Conformational memory in the association of the transmembrane protein phospholamban with the sarcoplasmic reticulum calcium pump SERCA.跨膜蛋白磷酸化酶结合蛋白与肌浆网钙泵 SERCA 相互作用的构象记忆。
J Biol Chem. 2017 Dec 29;292(52):21330-21339. doi: 10.1074/jbc.M117.794453. Epub 2017 Oct 29.
7
Structural basis for allosteric control of the SERCA-Phospholamban membrane complex by Ca and phosphorylation.钙和磷酸化对 SERCA-肌浆网钙转运蛋白磷酸酶膜复合物变构调控的结构基础
Elife. 2021 May 12;10:e66226. doi: 10.7554/eLife.66226.
8
The Phospholamban Pentamer Alters Function of the Sarcoplasmic Reticulum Calcium Pump SERCA.磷酸化肌浆网钙转运蛋白五聚体改变肌浆网钙泵 SERCA 的功能。
Biophys J. 2019 Feb 19;116(4):633-647. doi: 10.1016/j.bpj.2019.01.013. Epub 2019 Jan 22.
9
Time-resolved FRET reveals the structural mechanism of SERCA-PLB regulation.时间分辨荧光共振能量转移揭示 SERCA-PLB 调节的结构机制。
Biochem Biophys Res Commun. 2014 Jun 27;449(2):196-201. doi: 10.1016/j.bbrc.2014.04.166. Epub 2014 May 9.
10
Structural dynamics and topology of phosphorylated phospholamban homopentamer reveal its role in the regulation of calcium transport.磷酸化肌浆球蛋白结合蛋白同五聚体的结构动力学和拓扑结构揭示了其在钙转运调节中的作用。
Structure. 2013 Dec 3;21(12):2119-30. doi: 10.1016/j.str.2013.09.008. Epub 2013 Oct 24.
引用本文的文献
1
Nitroxyl (HNO) targets phospholamban cysteines 41 and 46 to enhance cardiac function.硝普钠（HNO）靶向肌球蛋白轻链磷酸酶靶蛋白（phospholamban）半胱氨酸 41 和 46 以增强心脏功能。
J Gen Physiol. 2019 Jun 3;151(6):758-770. doi: 10.1085/jgp.201812208. Epub 2019 Mar 6.
2
A bifunctional spin label reports the structural topology of phospholamban in magnetically-aligned bicelles.一种双功能自旋标记物报告了磁取向双分子层中受磷蛋白的结构拓扑。
J Magn Reson. 2016 Jan;262:50-56. doi: 10.1016/j.jmr.2015.12.005. Epub 2015 Dec 12.
3
Structural dynamics and topology of phosphorylated phospholamban homopentamer reveal its role in the regulation of calcium transport.磷酸化肌浆球蛋白结合蛋白同五聚体的结构动力学和拓扑结构揭示了其在钙转运调节中的作用。
Structure. 2013 Dec 3;21(12):2119-30. doi: 10.1016/j.str.2013.09.008. Epub 2013 Oct 24.
4
Determination of structural topology of a membrane protein in lipid bilayers using polarization optimized experiments (POE) for static and MAS solid state NMR spectroscopy.使用用于静态和 MAS 固态 NMR 光谱学的偏振优化实验 (POE) 测定脂质双层中膜蛋白的结构拓扑。
J Biomol NMR. 2013 Oct;57(2):91-102. doi: 10.1007/s10858-013-9766-2. Epub 2013 Aug 21.
5
Tuning the structural coupling between the transmembrane and cytoplasmic domains of phospholamban to control sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) function.调节磷蛋白与细胞质结构域之间的结构偶联，以控制肌浆网 Ca(2+)-ATP 酶（SERCA）的功能。
J Muscle Res Cell Motil. 2012 Dec;33(6):485-92. doi: 10.1007/s10974-012-9319-4. Epub 2012 Sep 13.
6
Multidimensional oriented solid-state NMR experiments enable the sequential assignment of uniformly 15N labeled integral membrane proteins in magnetically aligned lipid bilayers.多维定向固态 NMR 实验可实现对在磁场定向脂质双层中均匀 15N 标记的完整膜蛋白进行顺序赋值。
J Biomol NMR. 2011 Nov;51(3):339-46. doi: 10.1007/s10858-011-9571-8.
7
Proton evolved local field solid-state nuclear magnetic resonance using Hadamard encoding: theory and application to membrane proteins.采用哈达玛编码的质子演化局域场固态核磁共振：在膜蛋白中的理论与应用。
J Chem Phys. 2011 Aug 21;135(7):074503. doi: 10.1063/1.3622604.
本文引用的文献
1
A refinement protocol to determine structure, topology, and depth of insertion of membrane proteins using hybrid solution and solid-state NMR restraints.一种使用混合溶液和固态核磁共振约束来确定膜蛋白结构、拓扑结构和插入深度的优化方案。
J Biomol NMR. 2009 Aug;44(4):195-205. doi: 10.1007/s10858-009-9328-9. Epub 2009 Jul 14.
2
Structure and topology of monomeric phospholamban in lipid membranes determined by a hybrid solution and solid-state NMR approach.通过混合溶液和固态核磁共振方法确定脂质膜中单体受磷蛋白的结构和拓扑结构。
Proc Natl Acad Sci U S A. 2009 Jun 23;106(25):10165-70. doi: 10.1073/pnas.0904290106. Epub 2009 Jun 9.
3
Calcium and cardiomyopathies.钙与心肌病
Subcell Biochem. 2007;45:523-37. doi: 10.1007/978-1-4020-6191-2_20.
4
Structural and dynamic basis of phospholamban and sarcolipin inhibition of Ca(2+)-ATPase.受磷蛋白和肌浆脂质蛋白抑制的Ca(2+) -ATP酶的结构与动力学基础
Biochemistry. 2008 Jan 8;47(1):3-13. doi: 10.1021/bi701668v. Epub 2007 Dec 15.
5
The Ca2+ ATPase of cardiac sarcoplasmic reticulum: Physiological role and relevance to diseases.心肌肌浆网的Ca2+ ATP酶：生理作用及其与疾病的关联。
Biochem Biophys Res Commun. 2008 Apr 25;369(1):182-7. doi: 10.1016/j.bbrc.2007.11.161. Epub 2007 Dec 7.
6
Controlling the inhibition of the sarcoplasmic Ca2+-ATPase by tuning phospholamban structural dynamics.通过调节受磷蛋白的结构动力学来控制肌浆网Ca2 + -ATP酶的抑制作用。
J Biol Chem. 2007 Dec 21;282(51):37205-14. doi: 10.1074/jbc.M704056200. Epub 2007 Sep 30.
7
Spectroscopic validation of the pentameric structure of phospholamban.受磷蛋白五聚体结构的光谱验证
Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14676-81. doi: 10.1073/pnas.0701016104. Epub 2007 Sep 5.
8
Using low-E resonators to reduce RF heating in biological samples for static solid-state NMR up to 900 MHz.使用低损耗谐振器减少生物样品中的射频加热，用于高达900兆赫兹的静态固态核磁共振。
J Magn Reson. 2007 Mar;185(1):77-93. doi: 10.1016/j.jmr.2006.11.008. Epub 2006 Dec 14.
9
Concerted conformational effects of Ca2+ and ATP are required for activation of sequential reactions in the Ca2+ ATPase (SERCA) catalytic cycle.Ca2+ 与ATP的协同构象效应是Ca2+ -ATP酶（SERCA）催化循环中连续反应激活所必需的。
Biochemistry. 2006 Nov 21;45(46):13769-78. doi: 10.1021/bi061255d.
10
Reversal of calcium cycling defects in advanced heart failure toward molecular therapy.晚期心力衰竭中钙循环缺陷的逆转与分子治疗
J Am Coll Cardiol. 2006 Nov 7;48(9 Suppl 1):A15-23. doi: 10.1016/j.jacc.2006.06.070.
Zotero 插件