2MU9

Changing ABRA protein peptide to fit the HLA-DR B1*0301 molecule renders it protection-inducing

Summary for 2MU9

• Entry DOI: 10.2210/pdb2mu9/pdb
• NMR Information: BMRB: 25203
• Descriptor: P101/acidic basic repeat antigen (1 entity in total)
• Functional Keywords: acidic-basic repeat antigen (abra), peptide binding protein
• Biological source: Plasmodium falciparum
• Total number of polymer chains: 1
• Total formula weight: 2502.95

Authors

Salazar, L.,Alba, M.,Curtidor, H.,Bermudez, A.,Vargas, L.,Rivera, Z.,Patarroyo, M. (deposition date: 2014-09-04, release date: 2015-09-16, Last modification date: 2024-05-15)

Primary citation

Salazar, L.M.,Alba, M.P.,Curtidor, H.,Bermudez, A.,Vargas, L.E.,Rivera, Z.J.,Patarroyo, M.E.
Changing ABRA protein peptide to fit into the HLA-DRbeta1*0301 molecule renders it protection-inducing.
Biochem.Biophys.Res.Commun., 322:119-125, 2004

PubMed Abstract: The Plasmodium falciparum acidic-basic repeat antigen represents a potential malarial vaccine candidate. One of this protein's high activity binding peptides, named 2150 ((161)KMNMLKENVDYIQKNQNLFK(180)), is conserved, non-immunogenic, and non-protection-inducing. Analogue peptides whose critical binding residues (in bold) were replaced by amino-acids having similar mass but different charge were synthesized and tested to try to modify such immunological properties. These analogues' HLA-DRbeta1* molecule binding ability were also studied in an attempt to explain their biological mechanisms and correlate binding capacity and immunological function with their three-dimensional structure determined by (1)H NMR. A 3(10) distorted helical structure was identified in protective and immunogenic peptide 24922 whilst alpha-helical structure was found for non-immunogenic, non-protective peptides having differences in alpha-helical position. The changes performed on immunogenic, protection-inducing peptide 24922 allowed it to bind specifically to the HLA-DRbeta1*0301 molecule, suggesting that these changes may lead to better interaction with the MHC Class II-peptide-TCR complex rendering it immunogenic and protective, thus suggesting a new way of developing multi-component, sub-unit-based anti-malarial vaccines.

PubMed: 15313182
DOI: 10.1016/j.bbrc.2004.07.086

Experimental method

SOLUTION NMR