TY - JOUR
T1 - MHC allele-specific binding of a malaria peptide makes it become promiscuous on fitting a glycine residue into pocket 6
AU - Vargas, Luis Eduardo
AU - Parra, Carlos Alberto
AU - Salazar, Luz Mary
AU - Guzmán, Fanny
AU - Pinto, Martha
AU - Patarroyo, Manuel E.
PY - 2003/7/18
Y1 - 2003/7/18
N2 - Peptide 1585 (EVLYLKPLAGVYRSLKKQLE) has a highly conserved amino-acid sequence located in the Plasmodium falciparum main merozoite surface protein (MSP-1) C-terminal region, required for merozoite entry into human erythrocytes and therefore represents a vaccine candidate for P. falciparum malaria. Original sequence-specific binding to five HLA DRB1* alleles (0101, 0102, 0401, 0701, and 1101) revealed this peptide's specific HLA DRB1*0102 allele binding. This peptide's allele-specific binding to HLA DRB1*0102 took on broader specificity for the DRB1*0101, -0401, and -1101 alleles when lysine was replaced by glycine in position 17 (peptide 5198: EVLYLKPLAGVYRSLKG17QLE). Binding of the identified G10VYRSLKGQLE20 C-terminal register to these alleles suggests that peptide promiscuous binding relied on fitting Y12, L15, and G17 into P-1, P-4, and P-6, respectively. The implications of the findings and the future of this synthetic vaccine candidate are discussed.
AB - Peptide 1585 (EVLYLKPLAGVYRSLKKQLE) has a highly conserved amino-acid sequence located in the Plasmodium falciparum main merozoite surface protein (MSP-1) C-terminal region, required for merozoite entry into human erythrocytes and therefore represents a vaccine candidate for P. falciparum malaria. Original sequence-specific binding to five HLA DRB1* alleles (0101, 0102, 0401, 0701, and 1101) revealed this peptide's specific HLA DRB1*0102 allele binding. This peptide's allele-specific binding to HLA DRB1*0102 took on broader specificity for the DRB1*0101, -0401, and -1101 alleles when lysine was replaced by glycine in position 17 (peptide 5198: EVLYLKPLAGVYRSLKG17QLE). Binding of the identified G10VYRSLKGQLE20 C-terminal register to these alleles suggests that peptide promiscuous binding relied on fitting Y12, L15, and G17 into P-1, P-4, and P-6, respectively. The implications of the findings and the future of this synthetic vaccine candidate are discussed.
KW - Binding motifs
KW - Class II molecules
KW - HLA-DR molecules
KW - HLA-HLA DRB101 alleles
KW - MSP-1 peptide
KW - Peptide binding assays
KW - Plasmodium falciparum
KW - Pocket 6
KW - Promiscuous peptide
KW - Synthetic vaccines
UR - http://www.scopus.com/inward/record.url?scp=0038049454&partnerID=8YFLogxK
U2 - 10.1016/S0006-291X(03)01129-X
DO - 10.1016/S0006-291X(03)01129-X
M3 - Article
C2 - 12849994
AN - SCOPUS:0038049454
SN - 0006-291X
VL - 307
SP - 148
EP - 156
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -
