T1BT* structural study of an anti-plasmodial peptide through NMR and molecular dynamics.
T1BT* structural study of an anti-plasmodial peptide through NMR and molecular dynamics.
复制标题
DOI：
10.1186/1475-2875-12-104
复制
发表时间：
2013-03-18
期刊：
影响因子：
3
通讯作者：
Lehmann TE
中科院分区：
文献类型：
--
作者：
Topchiy E;Armstrong GS;Boswell KI;Buchner GS;Kubelka J;Lehmann TE
T1BT*是一种包含恶性疟原虫环孢子子蛋白（CSP）中心重复区5 ‘小重复和3 ’大重复T1和B表位以及位于同一蛋白c端通用T*表位的肽结构体。这种具有B = (NANP)3的肽结构已被发现在近交小鼠和远交非人灵长类动物中引发抗孢子子抗体和γ -干扰素筛选t细胞反应。另一方面，核磁共振和CD光谱鉴定出肽B ' = (NPNA)3是CSP中主要重复序列的结构单元，而不是更常见的NANP。为了评估NPNA节奏对已证实的抗疟原虫肽的结构影响，本研究确定了T1BT*和T1B t *的溶液结构。通过核磁共振波谱和分子动力学计算确定了T1BT*和T1B t *的溶液结构。对这些结构进行比较，以确定它们之间的主要异同。两种肽的结构完全不同，其中T1B t *具有强烈的螺旋倾向。核磁共振和CD数据，结合分子建模，提供了关于T1BT*和T1B t *拓扑结构的额外信息。了解引起适当免疫原性反应所需的肽结构有助于设计更有效的、构象确定的疟疾候选疫苗。如果从CSP衍生的肽需要具有螺旋结构才能有效地与相应的抗体相互作用，那么基于T1B t *结构的疫苗作为红细胞前疫苗应该具有更高的效率，可以防止孢子体感染肝细胞。
T1BT* is a peptide construct containing the T1 and B epitopes located in the 5’ minor repeat and the 3’ major repeat of the central repeat region of the Plasmodium falciparum circumsporozoite protein (CSP), respectively, and the universal T* epitope located in the C-terminus of the same protein. This peptide construct, with B = (NANP)3, has been found to elicit antisporozoite antibodies and gamma-interferon-screening T-cell responses in inbred strains of mice and in outbred nonhuman primates. On the other hand, NMR and CD spectroscopies have identified the peptide B’ = (NPNA)3 as the structural unit of the major repeat in the CSP, rather than the more commonly quoted NANP. With the goal of assessing the structural impact of the NPNA cadence on a proven anti-plasmodial peptide, the solution structures of T1BT* and T1B’T* were determined in this work. NMR spectroscopy and molecular dynamics calculations were used to determine the solution structures of T1BT* and T1B’T*. These structures were compared to determine the main differences and similarities between them. Both peptides exhibit radically different structures, with the T1B’T* showing strong helical tendencies. NMR and CD data, in conjunction with molecular modelling, provide additional information about the topologies of T1BT* and T1B’T*. Knowing the peptide structures required to elicit the proper immunogenic response can help in the design of more effective, conformationally defined malaria vaccine candidates. If peptides derived from the CSP are required to have helical structures to interact efficiently with their corresponding antibodies, a vaccine based on the T1B’T* construct should show higher efficiency as a pre-erythrocyte vaccine that would prevent infection of hepatocytes by sporozoites.
登录
查看更多内容
影响因子：
16.6
作者：
Pfeiffer, B;Peduzzi, E;Robinson, JA
通讯作者：
Robinson, JA
影响因子：
2.7
作者：
DELAGLIO, F;GRZESIEK, S;BAX, A
通讯作者：
BAX, A
影响因子：
3.1
作者：
Sarkar, Pralay K;Ahluwalia, Gautam;Talwar, Arunabh
通讯作者：
Talwar, Arunabh
影响因子：
2.9
作者：
MANNING, MC;WOODY, RW
通讯作者：
WOODY, RW
影响因子：
4.9
作者：
Ghasparian, A;Moehle, K;Robinson, JA
通讯作者：
Robinson, JA