Orientating Peptide Residues and Increasing the Distance between Pockets to Enable Fitting into MHC-TCR Complex Determine Protection against Malaria
详细信息 查看全文
- 作者：Gladys Cifuentes ; Fabiola Espejo ; Luis Eduardo Vargas ; Carlos Parra ; Magnolia Vanegas ; and Manuel Elkin Patarroyo
- 刊名：Biochemistry
- 出版年：2004
- 出版时间：June 1, 2004
- 年：2004
- 卷：43
- 期：21
- 页码：6545 - 6553
- 全文大小：218K
- 年卷期：v.43,no.21(June 1, 2004)
- ISSN：1520-4995
文摘
The erythrocyte binding antigen EBA-175 is a 175-kDa Plasmodium falciparum protein, whichhas been shown to be involved in the process of invasion of erythrocytes. It has been found that conservedpeptide 1818 belonging to this protein has high red blood cell binding capacity and plays an importantrole in the invasion process. This peptide is neither immunogenic nor protective. Peptide 1818 analogueshad some of their previously recognized critical red blood cell binding residues substituted for aminoacids having similar volume or mass but different polarity to make them fit into HLA-DR
beta2.gif" BORDER=0 ALIGN="middle">1*1101molecules; these 1818 peptide analogues were then synthesized and inoculated into Aotus nancymaaemonkeys, generating different immunogenic and/or protective immune responses. Short structures suchas 310-helix, classical, or distorted type-III beta2.gif" BORDER=0 ALIGN="middle">-turns were found in the immunogenic and protective peptidesonce the secondary structure had been analyzed by NMR and its structure correlated with its immunologicalproperties. These data suggest that peptide flexibility may lead to better fitting into immune systemmolecules, therefore making them excellent candidates for consideration as components of a subunit-based, multicomponent synthetic antimalarial vaccine.
beta2.gif" BORDER=0 ALIGN="middle">1*1101molecules; these 1818 peptide analogues were then synthesized and inoculated into Aotus nancymaaemonkeys, generating different immunogenic and/or protective immune responses. Short structures suchas 310-helix, classical, or distorted type-III beta2.gif" BORDER=0 ALIGN="middle">-turns were found in the immunogenic and protective peptidesonce the secondary structure had been analyzed by NMR and its structure correlated with its immunologicalproperties. These data suggest that peptide flexibility may lead to better fitting into immune systemmolecules, therefore making them excellent candidates for consideration as components of a subunit-based, multicomponent synthetic antimalarial vaccine.