Solution structure of an EGF module pair from the Plasmodium falciparum merozoite surface protein 1.
The solution structure of the 96-residue C-terminal fragment of the merozoite surface protein 1 (MSP-1) from Plasmodium falciparum has been determined using nuclear magnetic resonance (NMR) spectroscopic measurements on uniformly13C/15N-labelled protein, efficiently expressed in the methylotrophic yeast Komagataella (Pichia) pastoris. The structure has two domains with epidermal growth factor (EGF)-like folds with a novel domain interface for the EGF domain pair interactions, formed from a cluster of hydrophobic residues. This gives the protein a U-shaped overall structure with the N-terminal proteolytic processing site close to the C-terminal glycosyl phosphatidyl inositol (GPI) membrane anchor site, which is consistent with the involvement of a membrane-bound proteinase in the processing of MSP-1 during erythrocyte invasion. This structure, which is the first protozoan EGF example to be determined, contrasts with the elongated structures seen for EGF-module pairs having shared Ca2+-ligation sites at their interface, as found, for example, in fibrillin-1. Recognition surfaces for antibodies that inhibit processing and invasion, and antibodies that block the binding of these inhibitory antibodies, have been mapped on the three-dimensional structure by considering specific MSP-1 mutants.
Morgan
W D
WD
Molecular Structure Division, The Ridgeway Mill Hill, London, NW7 1AA, UK.
Birdsall
B
B
Frenkiel
T A
TA
Gradwell
M G
MG
Burghaus
P A
PA
Syed
S E
SE
Uthaipibull
C
C
Holder
A A
AA
Feeney
J
J
D000595:Amino Acid Sequence; D000818:Animals; D016384:Consensus Sequence; D004220:Disulfides / Q000032:analysis; D004815:Epidermal Growth Factor / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D020066:Merozoite Surface Protein 1 / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010963:Plasmodium falciparum; D010966:Plasmodium vivax / Q000737:chemistry; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012984:Software; D012996:Solutions
D004220:Disulfides; D020066:Merozoite Surface Protein 1; D012996:Solutions; D004815:Epidermal Growth Factor