Amino acid residues essential for biological activity of a peptide derived from a major histocompatibility complex class I antigen.
The stimulatory activity of peptides from the alpha 1 domain of the major histocompatibility complex (MHC) class I antigen on adipose cell glucose transport was previously shown to require a preformed, ordered conformation of the peptide. The two peptides studied previously were Dk-(61-85) (ERETQIAKGNEQSFRVDLRTLLRYY) and Dk-(69-85). We now show that systematic alanine substitution in Dk-(69-85) identifies residues that are essential for biological activity. Ordered structure of the peptides, estimated by circular dichroism, was found in all peptides with activity, but with a complex variety of spectra. Inactive peptides were in either a random coil or an ordered structure. Ordered structure, therefore, is not sufficient for activity. The peptides self-interact in the absence of cells and form aggregates that precipitate upon centrifugation. The tendency to aggregate is correlated with biological potency. Only MHC class I molecules have significant homology to the peptides studied here. The peptide self-interaction suggests that the biological effects in cells, which result from inhibition of receptor and transporter internalization, may be due to the binding (tantamount to self-interaction) of the peptide to the homologous sequences in the alpha 1 domain of the MHC class I molecule.
Stagsted
J
J
Receptron, Inc., Concord, CA 94520.
Mapelli
C
C
Meyers
C
C
Matthews
B W
BW
Anfinsen
C B
CB
Goldstein
A
A
Olsson
L
L
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D002942:Circular Dichroism; D004822:Epididymis; D005947:Glucose / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000494:pharmacology*; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011487:Protein Conformation; D051381:Rats; D013329:Structure-Activity Relationship
D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D010455:Peptides; D005947:Glucose