Comparison of the solution conformations of a cell-adhesive peptide LBE and its reverse sequence EBL.
Comparison of the solution conformations of a cell-adhesive peptide LBE and its reverse sequence EBL.
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细胞粘附肽 LBE 及其反向序列 EBL 的溶液构象比较。
DOI：
10.1080/07391102.1999.10508375
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Siahaan,TJ
中科院分区：
文献类型：
--
作者：
Jois,SD;Hughes,R;Siahaan,TJ
T细胞粘附由ICAM-1/LFA-1相互作用介导;这种相互作用在免疫应答期间的T细胞活化中起关键作用。来源于LFA-1的β亚基的LBE肽已经显示出抑制ICAM-1/LFA-1介导的T细胞粘附。本文采用NMR、CD和分子动力学模拟方法研究了LBE多肽及其反向序列（EBL）的溶液构象。反向肽已被用作生物学研究中的对照。将LBE序列逆转为EBL序列对它们各自构象的影响对于了解它们在体外和体内的生物学性质是重要的。在40%TFE/水中，两种肽均表现出螺旋构象。CD研究表明LBE呈现30%的螺旋构象，而EBL呈现20%的螺旋构象。从NMR和MD模拟研究，很明显，肽表现出稳定的螺旋构象，一个稳定的螺旋结构被发现在Leu 6至Leu 15的LBE和在Gly 9至Leu 17的EBL。LBE和EBL的螺旋构象可能与其他可能的构象平衡;其他构象包含环和转弯结构。两种肽都与二价阳离子结合，因为LBE来源于LFA-1的阳离子结合区。这项研究表明，逆转肽序列不会改变相应序列的二级结构。因此，在生物学研究中使用反向肽作为对照时必须谨慎。本研究将有助于我们设计更好的ICAM-1/LFA-1相互作用抑制剂。
T-cell adhesion is mediated by an ICAM-l/LFA-1 interaction; this interaction plays a crucial role in T-cell activation during immune response. LBE peptide, which is derived from the β-subunit of LFA-1, has been shown to inhibit ICAM-l/LFA-l-mediated T-cell adhesion. In this work, we studied the solution conformations of LBE peptide and its reverse sequence (EBL) by NMR, CD and molecular dynamics simulations. Reverse peptides have been used as controls in biological studies. The effect of reversing the sequence of LBE to EBL peptides on their respective conformations is important in understanding their biological propertiesin vitroorin vivo.The NMR studies for these peptides were carried out in water and in TFE/water solvent systems. In 40% TFE/water, both peptides exhibited helical conformation. CD studies suggested that the LBE exhibits 30% helical conformation, while the EBL exhibits 20% helical conformation. From the NMR and MD simulation studies, it was evident that the peptides exhibited a stable helical conformation; a stable helical structure was found at Leu6 to Leu 15 for LBE and at Gly9 to Leu 17 for EBL. The helical conformations of LBE and EBL may be in equilibrium with other possible conformers; the other conformers contain loop and turn structures. Both peptides bind to divalent cations because the LBE is derived from the cation-binding region of the LFA-1. This study shows that reversing the peptide sequence did not alter the secondary structure of the corresponding sequence. Hence, caution must be exercised when using reverse peptides as controls in biological studies. This report will improve our ability to design a better inhibitor of ICAM-l/LFA-1 interaction.