Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 7310 - 7320 |
| Number of pages | 11 |
| Journal | Biochemistry |
| Volume | 53 |
| Issue number | 46 |
| DOIs | |
| Publication status | Published - 2014 |
Cite this
}
Structure and dynamics of apical membrane antigen 1 from Plasmodium falciparum FVO. / Lim, San Sui; Yang, Wei W; Krishnarjuna, Bankala; Kannan Sivaraman, Komagal; Chandrashekaran, Indu Rajmohan; Kass, Itamar; MacRaild, Christopher Andrew; Devine, Shane; Debono, Cael; Anders, Robin F; Scanlon, Martin; Scammells, Peter John; Norton, Raymond Stanley; McGowan, Sheena.
In: Biochemistry, Vol. 53, No. 46, 2014, p. 7310 - 7320.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Structure and dynamics of apical membrane antigen 1 from Plasmodium falciparum FVO
AU - Lim, San Sui
AU - Yang, Wei W
AU - Krishnarjuna, Bankala
AU - Kannan Sivaraman, Komagal
AU - Chandrashekaran, Indu Rajmohan
AU - Kass, Itamar
AU - MacRaild, Christopher Andrew
AU - Devine, Shane
AU - Debono, Cael
AU - Anders, Robin F
AU - Scanlon, Martin
AU - Scammells, Peter John
AU - Norton, Raymond Stanley
AU - McGowan, Sheena
PY - 2014
Y1 - 2014
N2 - Apical membrane antigen 1 (AMA1) interacts with RON2 to form a protein complex that plays a key role in the invasion of host cells by malaria parasites. Blocking this protein-protein interaction represents a potential route to controlling malaria and related parasitic diseases, but the polymorphic nature of AMA1 has proven to be a major challenge to vaccine-induced antibodies and peptide inhibitors exerting strain-transcending inhibitory effects. Here we present the X-ray crystal structure of AMA1 domains I and II from Plasmodium falciparum strain FVO. We compare our new structure to those of AMA1 from P. falciparum 3D7 and Plasmodium vivax. A combination of normalized B factor analysis and computational methods has been used to investigate the flexibility of the domain I loops and how this correlates with their roles in determining the strain specificity of human antibody responses and inhibitory peptides. We also investigated the domain II loop, a key region involved in inhibitor binding, by comparison of multiple AMA1 crystal structures. Collectively, these results provide valuable insights that should contribute to the design of strain-transcending agents targeting P. falciparum AMA1.
AB - Apical membrane antigen 1 (AMA1) interacts with RON2 to form a protein complex that plays a key role in the invasion of host cells by malaria parasites. Blocking this protein-protein interaction represents a potential route to controlling malaria and related parasitic diseases, but the polymorphic nature of AMA1 has proven to be a major challenge to vaccine-induced antibodies and peptide inhibitors exerting strain-transcending inhibitory effects. Here we present the X-ray crystal structure of AMA1 domains I and II from Plasmodium falciparum strain FVO. We compare our new structure to those of AMA1 from P. falciparum 3D7 and Plasmodium vivax. A combination of normalized B factor analysis and computational methods has been used to investigate the flexibility of the domain I loops and how this correlates with their roles in determining the strain specificity of human antibody responses and inhibitory peptides. We also investigated the domain II loop, a key region involved in inhibitor binding, by comparison of multiple AMA1 crystal structures. Collectively, these results provide valuable insights that should contribute to the design of strain-transcending agents targeting P. falciparum AMA1.
UR - http://pubs.acs.org/doi/pdf/10.1021/bi5012089
U2 - 10.1021/bi5012089
DO - 10.1021/bi5012089
M3 - Article
VL - 53
SP - 7310
EP - 7320
JO - Biochemistry
JF - Biochemistry
SN - 0006-2960
IS - 46
ER -