Mitochondrial and microsomal ferric b5 cytochromes exhibit divergent conformational plasticity in the context of a common fold.
Mitochondrial and microsomal ferric b5 cytochromes exhibit divergent conformational plasticity in the context of a common fold.
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线粒体和微粒体铁 b5 细胞色素在共同折叠的背景下表现出不同的构象可塑性。
DOI：
10.1021/bi050564l
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Rivera,Mario
中科院分区：
文献类型：
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作者：
Simeonov,Mario;Altuve,Adriana;Massiah,MichaelA;Wang,An;Eastman,MargaretA;Benson,DavidR;Rivera,Mario
通过NMR光谱监测的天然状态氢氘交换（HDX）已被用于比较铁大鼠肝外线粒体膜细胞色素b5（rOMb 5）和铁牛肝微粒体细胞色素b5（bMcb 5）的构象可塑性。数据分析表明，rOMb 5是较低的构象灵活的蛋白质的时间尺度上探测的HDX实验。这些数据还表明，与Mcb 5相比，从OMb 5释放氯化血红素的动力学屏障高得多，这一特征可能在很大程度上是其不同功能特性的来源。具体地说，数据表明，在螺旋α4和α5，侧面的环窝藏轴向配体His 63的构象迁移率是相当多的限制在rOMb 5比bMcb 5。rOMb 5中α4和α5的较低构象柔性可以合理地归因于蛋白质的该区域中更广泛的疏水堆积，这是由OM细胞色素b5中的两个保守侧链堆积基序引起的[Altuve，A.，Wang，L.，美国，本森，D. R.，和里维拉，M.等人（2004）Biochem. Biophys. Res. Commun.314，602 - 609]。
Native-state hydrogen−deuterium exchange (HDX) monitored by NMR spectroscopy has been used to compare conformational plasticity in ferric rat liver outer mitochondrial membrane cytochromeb5(rOMb5) and ferric bovine liver microsomal cytochromeb5(bMcb5). Analysis of the data indicated that rOMb5is the less conformationally flexible protein on the time scale probed by the HDX experiments. The data also suggest a likely contributor to the much higher kinetic barrier for the release of hemin from OMb5s in comparison to Mcb5s, a characteristic that may be to a large extent the source of their divergent functional properties. Specifically, the data indicate that conformational mobility within helices α4 and α5, which flank the loop harboring axial ligand His63, is considerably more restricted in rOMb5than in bMcb5. The lower conformational flexibility of α4 and α5 in rOMb5can reasonably be attributed to more extensive hydrophobic packing in that region of the protein, arising from two conserved side chain packing motifs in OM cytochromeb5s [Altuve, A., Wang, L., Benson, D. R., and Rivera, M. (2004)Biochem. Biophys. Res. Commun.314, 602−609].