Conservation of structural motifs and antigenic diversity in the Plasmodium falciparum merozoite surface protein-3 (MSP-3)
Conservation of structural motifs and antigenic diversity in the Plasmodium falciparum merozoite surface protein-3 (MSP-3)
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DOI：
10.1016/s0166-6851(97)00130-8
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发表时间：
1997-12-01
影响因子：
1.5
通讯作者：
Anders, RF
中科院分区：
文献类型：
--
作者：
McColl, DJ;Anders, RF
裂殖子表面蛋白-3（MSP-3）是恶性疟原虫（Plasmodiumfalciparum）无性血期红细胞分裂体和裂殖子分泌的多态性抗原。MSP-3的一个突出结构特征是由具有共有序列AXXAXXX的三个串联重复的七肽组成的结构域。四个丙氨酸七重重复序列的三个嵌段被与七重重复序列无关的非重复序列的短片段分开。MSP-3的C-末端含有一个富含谷氨酸的结构域，随后是另一个类似于亮氨酸拉链基序的七肽重复序列。对来自四个恶性疟原虫分离株的MSP-3基因的分析表明，MSP-3中的多态性主要是由于七重复序列内和侧翼的预测多肽的N-末端一半中的序列多样性。编码丙氨酸七重复序列的基因区域的突变似乎有两种类型。非重复序列中的独特突变已经产生氨基酸取代和缺失，其导致MSP-3变体中的独特序列。相比之下，七肽编码序列中的突变在很大程度上是二态的，并且在三个七肽块中的每一个中聚集在一个或两个七肽中。尽管七肽结构域内部和侧翼存在多样性，但AXXAXXX基序是高度保守的，预测α-螺旋二级结构形成的序列的其他特征也是如此。重组蛋白和合成肽用于产生MSP-3保守区和可变区的抗血清。这些试剂与寄生虫抗原的差异反应性将丙氨酸七重重复结构域确定为MSP-3多肽中抗原多样性的位点。(C)1997年Elsevier Science B.V.
Merozoite surface protein-3 (MSP-3) is a secreted polymorphic antigen associated with erythrocytic schizonts and merozoites of Plasmodium falciparum asexual blood-stages. A prominent structural feature of MSP-3 is a domain composed of three blocks of tandemly-repeated heptads with the consensus sequence AXXAXXX. The three blocks of four alanine heptad-repeats are separated by short stretches of non-repetitive sequence unrelated to the heptad-repeat. C-terminal to the heptad-repeats, MSP-3 contains a glutamic acid-rich domain followed by another heptad-repeat similar to a leucine-zipper motif. An analysis of the msp-3 gene from four P. falciparum isolates shows that polymorphism in MSP-3 is predominantly due to sequence diversity in the N-terminal half of the predicted polypeptide within and flanking the heptad-repeats. Mutations in the region of the gene that encodes the alanine heptad-repeats appear to be of two types. Unique mutations in non-repetitive sequence have generated amino acid substitutions and deletions that result in unique sequences among MSP-3 variants. In contrast, mutations in the heptad-coding sequence are largely dimorphic and are clustered in one or two heptads in each of the three blocks of heptads. Despite the diversity within and flanking the heptad domain the AXXAXXX motif is highly conserved as are other features of the sequence that predict the formation of alpha-helical secondary structure. Recombinant proteins and a synthetic peptide were used to raise antisera to conserved and variable regions of MSP-3. Differential reactivity of these reagents with the parasite antigen identified the alanine heptad-repeat domain as a site of antigenic diversity among MSP-3 polypeptides. (C) 1997 Elsevier Science B.V.