Conformational analysis of the immunodominant epitopes of the circumsporozoite protein of Plasmodium falciparum and knowlesi.
Conformational analysis of the immunodominant epitopes of the circumsporozoite protein of Plasmodium falciparum and knowlesi.
复制标题
恶性疟原虫和诺氏疟原虫环子孢子蛋白免疫显性表位的构象分析。
DOI：
10.1002/bip.360290117
复制
发表时间：
1990
期刊：
影响因子：
2.9
通讯作者：
Schlesinger,DH
中科院分区：
文献类型：
--
作者：
Fasman,GD;Park,K;Schlesinger,DH
疟原虫子孢子和裂殖子阶段的所有外壳蛋白，迄今为止，都含有串联重复序列，其中大多数含有至少一个脯氨酸残基。这些串联重复的环孢子体（CS）蛋白片段的P。恶性疟原虫P. KnowlesI已被证明构成免疫显性表位。这些肽段的抗体已被证明是保护性的，并导致CS蛋白的脱落，称为CSP反应。在本研究中，通过固相肽合成制备了四种合成肽。第一个肽对应于P的CS蛋白中的四肽串联重复。恶性疟原虫，重复8次，（NANP）8。第二种肽是第一种肽的类似物，其中甘氨酸取代脯氨酸，（NANG）8。第三个肽对应于P的串联重复。knowlesi，PK（1-24），重复两次（QAQGDGANAGQP）2。第四个肽是四肽重复序列，对应于PK（1-24）的C末端四肽，重复8次，（AGQP）8。CD测量显示，在水性介质中，相对于（NANG）8和PK（1-24）肽的重复序列，这些重复序列中脯氨酸的存在诱导（NANP）8肽中β折叠（β转角）含量的增加。（AGQP）8肽在合成肽中具有最高的β折叠（β转角）含量。它的结论是，这种增加在定义的结构相关，因此可能有助于增加这些重复的抗原性。
All of the coat proteins of the sporozoite and merozoite stages ofPlasmodium, determined to date, contain tandem repeats and most of these contain at least one proline residue. These tandemly repeated segments of the circumsporozite (CS) proteins ofP. falciparumandP. knowlesihave been shown to constitute an immunodominant epitope. Antibodies to these peptide segments have been shown to be protective and cause the shedding of the CS protein, known as the CSP reaction. In this study, four synthetic peptides were prepared by solid‐phase peptide synthesis. The first peptide corresponds to the tetrapeptide tandem repeat in the CS protein ofP. falciparum, repeated eight times, (NANP)8. The second peptide is an analogue of the first in which glycine is substituted for proline, (NANG)8. The third peptide corresponds to the tandem repeat ofP. knowlesi, PK(1–24), which is repeated twice (QAQGDGANAGQP)2. The fourth peptide is a tetrapeptide repeat, corresponding to the C‐terminal tetrapeptide of PK(1–24) and is repeated eight times, (AGQP)8. It is shown by CD measurements that the presence of proline in these repeats induces an increase in β‐sheet (β‐turn) content in the (NANP)8peptide relative to the repeat of (NANG)8and PK(1–24) peptide in aqueous media. The (AGQP)8peptide has the highest β‐sheet (β‐turn) content in the synthetic peptides. It is concluded that this increase in defined structure correlates well with and hence may contribute to the increased antigenicity in these repeats.