Plasmodium falciparum merozoite surface protein 2 is unstructured and forms amyloid-like fibrils.
Several merozoite surface proteins are being assessed as potential components of a vaccine against Plasmodium falciparum, the cause of the most serious form of human malaria. One of these proteins, merozoite surface protein 2 (MSP2), is unusually hydrophilic and contains tandem sequence repeats, characteristics of intrinsically unstructured proteins. A range of physicochemical studies has confirmed that recombinant forms of MSP2 are largely unstructured. Both dimorphic types of MSP2 (3D7 and FC27) are equivalently extended in solution and form amyloid-like fibrils although with different kinetics and structural characteristics. These fibrils have a regular underlying beta-sheet structure and both fibril types stain with Congo Red, but only the FC27 fibrils stain with Thioflavin T. 3D7 MSP2 fibrils seeded the growth of fibrils from 3D7 or FC27 MSP2 monomer indicating the involvement of a conserved region of MSP2 in fibril formation. Consistent with this, digestion of fibrils with proteinase K generated resistant peptides, which included the N-terminal conserved region of MSP2. A monoclonal antibody that reacted preferentially with monomeric recombinant MSP2 did not react with the antigen in situ on the merozoite surface. Glutaraldehyde cross-linking of infected erythrocytes generated MSP2 oligomers similar to those formed by polymeric recombinant MSP2. We conclude that MSP2 oligomers containing intermolecular beta-strand interactions similar to those in amyloid fibrils may be a component of the fibrillar surface coat on P. falciparum merozoites.
Adda
Christopher G
CG
Department of Biochemistry, La Trobe University, Victoria 3086, Australia.
Murphy
Vince J
VJ
Sunde
Margaret
M
Waddington
Lynne J
LJ
Schloegel
Jesse
J
Talbo
Gert H
GH
Vingas
Kleo
K
Kienzle
Vivian
V
Masciantonio
Rosella
R
Howlett
Geoffrey J
GJ
Hodder
Anthony N
AN
Foley
Michael
M
Anders
Robin F
RF
D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D006801:Humans; D016778:Malaria, Falciparum / Q000276:immunology / Q000469:parasitology*; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology
D000682:Amyloid; D000953:Antigens, Protozoan; D015800:Protozoan Proteins; C065974:merozoite surface protein 2, Plasmodium