Preparation, crystallization and preliminary X-ray analysis of a complex between the Plasmodium vivax sexual stage 25 kDa protein Pvs25 and a malaria transmission-blocking antibody Fab fragment.
The Plasmodium vivax sexual stage 25 kDa protein Pvs25, located on the surface of the ookinete form of the parasite, is a vaccine candidate designed to elicit immunity that blocks the transmission of malaria by mosquitoes. The 2A8 murine monoclonal antibody directed against recombinant Pvs25 prevents the formation of P. vivax oocysts in mosquitoes fed in the laboratory. The complex between recombinant Pvs25 and the Fab fragment of 2A8 forms crystals that diffract X-rays to 3.5 A. Two native data sets, A and B, have been collected from crystals of the Pvs25-Fab complex. Both crystals belong to space group P2(1), with unit-cell parameters of a = 86.3, b = 61.7, c = 142.7 A, beta = 101.7 degrees for data set A and a = 86.8, b = 61.0, c = 149.3 A, beta = 104.3 degrees for data set B, and contain two complex molecules per asymmetric unit. Efforts are under way to reveal the structure of the Pvs25-Fab complex by molecular replacement. The three-dimensional structure of the Pvs25-Fab complex will provide an understanding of the interaction between Pvs25 and the 2A8 antibody that inhibits ookinete development in the mosquito and should aid in the development of transmission-blocking vaccines against P. vivax malaria.
Saxena
Ajay K
AK
Structural Biology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Twinbrook II, 12441 Parklawn Drive, Rockville, Maryland 20852, USA.
Singh
Kavita
K
Long
Carole A
CA
Garboczi
David N
DN
D000818:Animals; D000913:Antibodies, Protozoan / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D000936:Antigen-Antibody Complex / Q000737:chemistry / Q000276:immunology; D002850:Chromatography, Gel; D003460:Crystallization; D018360:Crystallography, X-Ray; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D016780:Malaria, Vivax / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D010966:Plasmodium vivax / Q000737:chemistry* / Q000276:immunology*; D015800:Protozoan Proteins / Q000737:chemistry* / Q000276:immunology* / Q000302:isolation & purification
D000913:Antibodies, Protozoan; D000936:Antigen-Antibody Complex; D007140:Immunoglobulin Fab Fragments; D015800:Protozoan Proteins; C064783:sexual stage specific protein, Plasmodium