Gibson K D, Scheraga H A
Proc Natl Acad Sci U S A. 1986 Aug;83(15):5649-53. doi: 10.1073/pnas.83.15.5649.
The circumsporozoite protein of the human malaria parasite Plasmodium falciparum contains multiple tandem repeats of the amino acid sequence Asn-Ala-Asn-Pro. The repeated sequence encompasses the immunodominant region of the protein, and antibodies raised against it are potent inhibitors of invasion and development of sporozoites in cultured hepatocytes. Using a modified build-up procedure, we have explored a large number of possible helical and near-helical conformations of a terminally blocked tetraicosapeptide, consisting of six repeats of the sequence Asn-Ala-Asn-Pro, and conclude that two helical conformations are energetically favored to the exclusion of all others. One of these conformations is longer, thinner, and left-handed and is likely to be adopted in nonpolar environments, while the other is shorter, broader, and right-handed and should be favored in aqueous solutions. We propose that the immunodominant region of the circumsporozoite protein of P. falciparum adopts one of these conformations in vivo.
人类疟原虫恶性疟原虫的环子孢子蛋白含有氨基酸序列天冬酰胺-丙氨酸-天冬酰胺-脯氨酸的多个串联重复序列。重复序列涵盖了该蛋白的免疫显性区域，针对该区域产生的抗体是培养肝细胞中子孢子入侵和发育的有效抑制剂。我们采用一种改进的构建方法，探索了一种末端封闭的二十四肽（由六个天冬酰胺-丙氨酸-天冬酰胺-脯氨酸序列重复组成）的大量可能的螺旋和近螺旋构象，并得出结论，两种螺旋构象在能量上比其他构象更受青睐。其中一种构象更长、更细且为左手螺旋，可能在非极性环境中采用，而另一种构象更短、更宽且为右手螺旋，在水溶液中应该更受青睐。我们提出，恶性疟原虫环子孢子蛋白的免疫显性区域在体内采用这些构象之一。
