Structural origin of the immunological diversity of two closely related tetrapeptides: CIDNP study of TyrTyrGluGlu and TyrGluTyrGlu epitopes.
Photochemically induced dynamic nuclear polarization (photoCIDNP) measurements, specific for exposed tyrosine residues, have been applied to elucidate conformational differences responsible for the immunological diversity of the synthetic multichain copolymers, Tyr1Tyr2Glu3Glu4-poly-DL-Ala-poly-Lys and Tyr1Glu2Tyr3Glu4-poly-DL-Ala-poly-LS. These two copolymers are essentially identical in their molecular weight, size, shape and composition, and differ only in the order of the two internal amino acid residues within the sequence of the tetrapeptide epitopes. Nonetheless, previous studies have shown that the two macromolecules behave differently, as evidenced by their immunological and immunogenic properties. As immunogens they act under different genetic control mechanisms, and differ in their interactions with antigen presenting cells, T cells and B cells. Antibodies elicited against these two antigens do not cross react. The photoCIDNP measurements of these two polymers, intended to elucidate discrete structural differences controlling immune recognition, showed that in the TyrTyrGluGlu polymer, Tyr1 and Tyr2 rings are free, non-interacting and undergo fast internal rotation. Computed minimum energy conformations confirm these conclusions and indicate that Tyr1 and Tyr2 point to different regions in space. In TyrGluTyrGlu, however, CIDNP measurements give rise to one broad tyrosine 3,5 proton signal, the result of a strong Tyr1-Tyr3 hydrophobic interaction. These two tyrosine residues are thus close in space, and undergo slow internal rotation. These results are in agreement with the computed minimum energy conformations.
Muszkat
K A
KA
Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel.
Schechter
B
B
Sela
M
M
D000595:Amino Acid Sequence; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology; D005971:Glutamates / Q000737:chemistry*; D018698:Glutamic Acid; D007120:Immunochemistry / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000276:immunology; D010777:Photochemistry; D011487:Protein Conformation; D014443:Tyrosine / Q000737:chemistry*
D000939:Epitopes; D005971:Glutamates; D010455:Peptides; D018698:Glutamic Acid; D014443:Tyrosine