Flexibility of amino acid residues at position four of nonapeptides enhances their binding to human leucocyte antigen (HLA) molecules.
The binding affinity of synthetic nonapeptides to human leucocyte antigens (HLA) molecules of the A0201 allotype, the most common in Caucasian, is enhanced or reduced by suitable amino acid substitutions at position 4, as a result of increased or decreased chain flexibility. A higher flexibility of the bond at this position correlates with an easier accommodation of the fragment into the HLA groove, while rigidity of the peptide chain appears to interfere. These data are based on two lines of evidence: a) most natural high affinity ligands for HLA-A0201 possess, at position 4, flexible residues b) substitutions of such residues by rigid amino acids results in a decrease of binding affinity.
Chersi
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A
Istituto Regina Elena for Cancer Research, Laboratory of Biochemistry, CRS, Roma, Italy. biochimica@crs.ifo.it
di Modugno
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F
Rosano
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L
D000595:Amino Acid Sequence; D001665:Binding Sites; D015234:HLA-A Antigens / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D009842:Oligopeptides / Q000737:chemistry*; D011487:Protein Conformation; D044465:White People
D015234:HLA-A Antigens; D009842:Oligopeptides