Ca 2+-induced self-assembly in designed peptides with optimally spaced gamma-carboxyglutamic acid residues.
Ca 2+-induced self-assembly in designed peptides with optimally spaced gamma-carboxyglutamic acid residues.
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DOI：
10.1016/j.jinorgbio.2010.10.002
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发表时间：
2011-01
影响因子：
3.9
通讯作者：
Castellino, Francis J.
中科院分区：
文献类型：
--
作者：
Dai, Qiuyun;Dong, Mingxin;Liu, Zhuguo;Prorok, Mary;Castellino, Francis J.
我们先前已经阐明了天然含γ-羧基谷氨酸（Gla）的芋螺素（con）肽类中金属离子诱导的螺旋-螺旋组装的新范例，典型的是con-G和con-T的变体con-T[K7 Gla]。与疏水效应无关。在这些“金属拉链”结构中，Gla残基以i，i + 4，i + 7，i + 11间隔排列，这类似于卷曲螺旋的典型七元组中a和d残基的排列，与Ca 2+配位并形成特异性的反平行螺旋二聚体。为了评估Gla残基在肽自组装中的共同作用，我们在本文中将相同的Gla排列扩展到设计的肽：NH 2-（γLSγEAK）3-CONH 2（肽1）和NH 2-γLSγEAKγLSγQANγLSγ KAE-CONH 2（肽2）。肽1和肽2单独不显示螺旋性，但在多种二价阳离子存在下经历结构转变为螺旋构象。沉降平衡超浓缩分析表明，肽1和肽2在Ca ~（2+）存在下形成螺旋二聚体，而在Mg ~（2+）存在下不形成螺旋二聚体。含Cys的肽变体的折叠和巯基-二硫键重排分析表明，螺旋二聚体是反平行和平行二聚体的混合物，这与con-G和con-T[K7γGla]二聚体严格的反平行链取向不同。这些发现表明，Gla排列，i，i + 4，i + 7，i + 11，i + 14，在螺旋形成中起关键作用，而不严格遵守螺旋二聚体的链取向。
We have previously elucidated a new paradigm for the metal ion-induced helix-helix assembly in the natural γ-carboxyglutamic acid (Gla)-containing class of conantokin (con) peptides, typified by con-G and a variant of con-T, con-T[K7Gla]. independent of the hydrophobic effect. In these “metallo-zipper” structures, Gla residues spaced at i, i + 4, i + 7, i + 11 intervals, which is similar to the arrangement of a and d residues in typical heptads of coiled-coils, coordinate with Ca2+ and form specific antiparallel helical dimers. In order to evaluate the common role of Gla residues in peptide self-assembly, we extend herein the same Gla arrangement to designed peptides: NH2-(γLSγEAK)3-CONH2 (peptide 1) and NH2–γLSγEAKγLSγQANγLSγKAE–CONH2 (peptide 2). Peptide 1 and peptide 2 exhibit no helicity alone, but undergo structural transitions to helical conformations in the presence of a variety of divalent cations. Sedimentation equilibrium ultracenrifugation analyses showed that peptide 1 and peptide 2 form helical dimers in the presence of Ca2+, but not Mg2+, Folding and thiol-disulfide rearrangement assays with Cys-containing peptide variants indicated that the helical dimers are mixtures of antiparallel and parallel dimers, which is different from the strict antiparallel strand orientations of con-G and con-T[K7γGla] dimers. These findings suggest that the Gla arrangement, i, i + 4, i + 7, i + 11, i + 14, plays a key role in helix formation, without a strict adherence to strand orientation of the helical dimer.
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影响因子：
2.9
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CHEN, YH;YANG, JT;MARTINEZ, HM
通讯作者：
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通讯作者：
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影响因子：
2.9
作者：
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通讯作者：
Prorok, M