Exploring the positional importance of aromatic residues and lysine in the interactions of peptides with the Plasmodium falciparum Hsp70-1.
Plasmodium falciparum harbors an essential relict plastid called the apicoplast that is involved in several important biosynthetic processes. Over 500 nuclear encoded proteins are imported into the organelle that is now recognized as an important therapeutic target. These proteins contain an N-terminal transit peptide sequence essential for apicoplast targeting during which the P. falciparum Hsp70-1 plays an important role. In the present study, we have focused on the in vitro interactions of PfHsp70-1 with synthetic peptides endowed with transit peptide like features. The peptides exhibit higher affinity for PfHsp70-1 in the presence of ADP compared to ATP. The results highlight the positional importance of selected residues in the designed peptides for affinity. They suggest that better peptide affinity for the protein requires a Lys at second position, retention of aromatic residue at the last position, and absence of acidic residues at any position in the transit peptides. Overall, the present work is the first in vitro fluorescence-based study of PfHsp70-1 with peptides possessing transit peptide-like features.
Misra
Gauri
G
Central Drug Research Institute, CSIR, Lucknow, India.
Ramachandran
Ravishankar
R
D000244:Adenosine Diphosphate / Q000737:chemistry; D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry*; D007700:Kinetics; D008239:Lysine / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D010963:Plasmodium falciparum / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D013050:Spectrometry, Fluorescence / Q000379:methods
D018840:HSP70 Heat-Shock Proteins; D010455:Peptides; C081884:heat-shock protein 70.1; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D016650:Fluorescein-5-isothiocyanate; D008239:Lysine