Conformational studies of the synthetic precursor-specific region of preproparathyroid hormone.
Conformational studies of the synthetic precursor-specific region of preproparathyroid hormone.
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前甲状旁腺激素合成前体特异性区域的构象研究。
DOI：
10.1073/pnas.77.7.3983
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发表时间：
1980
影响因子：
11.1
通讯作者：
Fasman,GD
中科院分区：
文献类型：
--
作者：
Rosenblatt,M;Beaudette,NV;Fasman,GD
研究了代表前甲状旁腺激素原的NH 2-末端、受体特异性延伸序列的合成肽的二级结构。NH 2-末端延伸，或前导序列，可能在决定和促进蛋白质的细胞分泌中起关键作用。这些前体区域，包括所研究的合成激素片段，共享氨基酸序列的共同特征，并且在二级结构上也可能相似。如所述预测合成前体肽的二级结构[Chou，P. Y. & Fasman，G. D.（1978）Adv. Enzymol. 47，45-148]。二级结构来自圆二色光谱在生理pH的水性缓冲液中，并在非极性溶剂中选择近似的膜内环境。观察到两种高度结构化的构象。在水性缓冲液中，二级结构为27% α-螺旋、43% β-折叠和30%无规卷曲。在非极性溶剂中，二级结构为46% α-螺旋，0% β-折叠和54%无规卷曲。这些发现与从氨基酸序列预测的两个概率最高的结构相关。这种大小的肽（30个氨基酸）的二级结构含量相对较高，从水溶液到非极性环境的变化中观察到的构象转变可能反映了对NH 2-末端延伸序列的生理功能至关重要的结构特性，并且两者都与当前关于前体区域在蛋白质的细胞内运输和分泌中的作用的理论一致。
the secondary structure of a synthetic peptide representing the NH2-terminal, precursor-specific extension sequence of preproparathyroid hormone was studied. NH2-terminal extensions, or leader sequences, may serve a critical role in determining and facilitating the cellular secretion of proteins. These precursor regions, including the synthetic hormonal fragment studied, share common features of amino acid sequence and also may be similar in secondary structure. The secondary structure of the synthetic precursor peptide was predicted as described [Chou, P. Y. & Fasman, G. D. (1978) Adv. Enzymol. 47, 45-148]. The secondary structure was derived from circular dichroism spectra in both an aqueous buffer at physiological pH and in a nonpolar solvent selected to approximate the intramembranous environment. Two highly structured conformations were observed. In the aqueous buffer the secondary structure was 27% alpha-helix, 43% beta-sheet, and 30% random coil. In the nonpolar solvent the secondary structure was 46% alpha-helix, 0% beta-sheet, and 54% random coil. These findings correlated well with the two highest-probability structures predicted from the amino acid sequence. Both the relatively high content of secondary structure in a peptide of this size (30 amino acids) and the conformational transition observed in changing from aqueous to nonpolar environments may reflect structural properties critical to the physiological function of NH2-terminal extension sequences, and both are consistent with current theories regarding the role of precursor regions in the intracellular transport and secretion of proteins.