Surface properties of an amphiphilic peptide hormone and of its analog: corticotropin-releasing factor and sauvagine.
Surface properties of an amphiphilic peptide hormone and of its analog: corticotropin-releasing factor and sauvagine.
复制标题
两亲肽激素及其类似物的表面特性：促肾上腺皮质激素释放因子和索瓦吉尼。
DOI：
10.1073/pnas.80.23.7070
复制
发表时间：
1983
影响因子：
11.1
通讯作者：
Kézdy,FJ
中科院分区：
文献类型：
--
作者：
Lau,SH;Rivier,J;Vale,W;Kaiser,ET;Kézdy,FJ
合成促肾上腺皮质激素（促肾上腺皮质激素）释放因子[CRF；对于序列，参见 Vale, W., Spiess, J., Rivier, C. & Rivier, J. (1981) Science 213, 1394-1397] 在水溶液中主要以无规卷曲形式存在。当浓度大于 1 µM 时，肽表现出自聚集趋势，同时通过圆二色光谱测量，表观 α 螺旋含量略有增加。该分子形成的 α 螺旋具有高度两亲性，即亲水区域和疏水区域在螺旋的相对面上分离。正如从潜在的两亲结构预测的那样，CRF 强烈地结合到单个双层卵磷脂酰胆碱囊泡的表面。这种结合似乎遵循简单的 Langmuir 等温线，具有以下参数：Kd = 1.3 +/- 0.6 X 10(-7) M，饱和容量 (N) = 11.0 +/- 1.0 mmol 肽/mol 磷脂。 CRF 还很容易在空气-水界面形成不溶性单层。单层由具有分子区域的激素单体组成，每个氨基酸 A'0 = 22 A2，表明具有紧凑的二级结构。从单层的塌陷压力（19.0 +/- 0.1 达因/厘米；1 达因 = 10 微牛）判断，CRF 的两亲性接近血浆载脂蛋白，这是一类具有最明显两亲特征的蛋白质。这些结果表明，CRF 与细胞膜的结合伴随着α螺旋二级结构的诱导，并且正是这种主要的螺旋形式是肽的生物活性形式。
Synthetic corticotropin (adrenocorticotropic hormone)-releasing factor [CRF; for the sequence, see Vale, W., Spiess, J., Rivier, C. & Rivier, J. (1981) Science 213, 1394-1397] in aqueous solution exists predominantly as a random coil. At concentrations greater than 1 microM, the peptide shows a tendency to self-aggregate with a concurrent slight increase in the apparent alpha-helical content as measured by the CD spectrum. The alpha-helix formed by this molecule is highly amphiphilic--i.e., the hydrophilic and hydrophobic regions are segregated on opposite faces of the helix. As predicted from the potential amphiphilic structure, CRF binds avidly to the surface of single bilayer egg phosphatidylcholine vesicles. This binding appears to obey a simple Langmuir isotherm with the following parameters: Kd = 1.3 +/- 0.6 X 10(-7) M and capacity at saturation (N) = 11.0 +/- 1.0 mmol of peptide per mol of phospholipid. CRF also readily forms an insoluble monolayer at the air-water interface. The monolayer is composed of monomers of the hormone with molecular areas, A'0 = 22 A2 per amino acid, suggesting a compact secondary structure. Judged from the collapse pressure (19.0 +/- 0.1 dyne/cm; 1 dyne = 10 microN) of the monolayer, the amphiphilicity of CRF approximates that of plasma apolipoproteins, a class of proteins of the most pronounced amphiphilic character. These results suggest that the binding of CRF to the cell membrane is accompanied by the induction of an alpha-helical secondary structure and it is this predominantly helical form that is the biologically active form of the peptide.