2MTY

3D structure determination of STARP peptides implicated in P. falciparum Invasion of hepatic cells

2MTY の概要

• エントリーDOI: 10.2210/pdb2mty/pdb
• 関連するPDBエントリー: 2MU6
• NMR情報: BMRB: 25191
• 分子名称: STARP antigen (1 entity in total)
• 機能のキーワード: starp, sporozoite, malaria vaccine, peptide binding
• 由来する生物種: Plasmodium falciparum
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 2332.59

構造登録者

Bermudez, A.,Alba, M.P.,Vanegas, M.,Patarroyo, M.E. (登録日: 2014-09-01, 公開日: 2014-12-17, 最終更新日: 2024-05-15)

主引用文献

Bermudez, A.,Alba, M.P.,Vanegas, M.,Patarroyo, M.E.
3D structure determination of STARP peptides implicated in P. falciparum invasion of hepatic cells.
Vaccine, 28:4989-4996, 2010

PubMed Abstract: To block the different stages of Plasmodium falciparum invasion into human hepatocytes and red blood cells, we have focused on those proteins belonging to the pre-erythrocytic stage. One of these proteins is Sporozoite Threonine and Asparagine Rich Protein (STARP), which is a ligand used by P. falciparum parasites to bind Hepatic cells (HepG2). Previous studies on this protein identified two conserved peptides binding with high activity to HepG2 cells (namely 20546 and 20570) with corresponding critical hepatic-cell binding residues and determined an important role for these two peptides in the invasion process. This study shows the results of immunization trials in Aotus monkeys with native STARP peptides and analogues modified in critical hepatic-cell binding residues. The results show that native peptides are not immunogenic but can induce high-antibody titers when their critical residues are replaced by other with similar volume and mass but different polarity. Nuclear Magnetic Resonance ((1)H NMR) studies revealed that native peptides (non-immunogenic) displayed shorter alpha-helical regions compared to their highly immunogenic modified analogues. Binding assays with HLA-DRbeta1* molecules showed that 20546 modified peptides inducing high-antibody titers (24972, 24320 and 24486) bound to HLA-DRbeta1*0301 molecules, while the 20570 modified analogue (24322) bound to HLA-DRbeta1*0101. The results support including these high-immunogenic STARP-derived modified peptides as pre-erythrocytic candidates to be included in the design of a synthetic antimalarial vaccine.

PubMed: 20580741
DOI: 10.1016/j.vaccine.2010.05.025

実験手法

SOLUTION NMR