Transformation of an α-helix peptide into a β-hairpin induced by addition of a fragment results in creation of a coexisting state
Transformation of an α-helix peptide into a β-hairpin induced by addition of a fragment results in creation of a coexisting state
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DOI：
10.1002/prot.21263
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发表时间：
2007-03-01
影响因子：
2.9
通讯作者：
Tamura, Atsuo
中科院分区：
文献类型：
--
作者：
Araki, Mitsugu;Tamura, Atsuo
决定蛋白质三级结构的内在规则一直是未知的，部分原因是有助于蛋白质结构稳定的物理化学因素不能表示为局部相互作用的线性组合。为了阐明蛋白质中非局部相互作用引起的非线性项的规则，我们试图通过在TP的C末端添加7个残基，将具有完全螺旋结构的肽（Target Peptide或TP）转化为具有P-发夹结构的肽（Designed Peptide或DP）。根据核磁共振测量的分析，虽然P-发夹结构在一些DP中是稳定的，但很明显，在TP中观察到的螺旋结构也是持久的，甚至延伸到整个分子的长度。因此，我们已经产生了一种肽分子，其以几乎相等的填充水平包含α-螺旋和P-发夹构象。这些DP中所含的螺旋结构比TP中的螺旋更稳定，这表明稳定一种构象不会导致另一种构象不稳定。因此，这些DP可以被认为是变色龙序列的分离的肽版本，其具有根据蛋白质结构中周围环境的背景改变二级结构的能力。一个二级结构的转变引起了原始结构和诱导结构的稳定，这一事实将揭示蛋白质折叠的机制。
Intrinsic rules of determining the tertiary structure of a protein have been unknown partly because physicochemical factors that contribute to stabilization of a protein structure cannot be represented as a linear combination of local interactions. To clarify the rules on the nonlinear term caused by nonlocal interaction in a protein, we tried to transform a peptide that has a fully helical structure (Target Peptide or TP) into a peptide that has a P-hairpin structure (Designed Peptide or DP) by adding seven residues to the C terminus of TP. According to analyses of nuclear magnetic resonance measurements, while the P-hairpin structure is stabilized in some DPs, it is evident that the helical structure observed in TP is also persistent and even extended throughout the length of the molecule. As a result, we have produced a peptide molecule that contains both the a-helix and P-hairpin conformation at an almost equally populated level. The helical structures contained in these DPs were more stable than the helix in TP, suggesting that stabilizing one conformation does not result in destabilizing the other conformation. These DPs can thus be regarded as an isolated peptide version of the chameleon sequence, which has the capability of changing the secondary structure depending on the context of the surrounding environment in a protein structure. The fact that the transformation of one secondary structure caused stabilization of both the original and the induced structure would shed light on the mechanism of protein folding.