A possible receptor-binding function for the N-terminus of connective tissue activating peptide III.
Connective tissue activating peptide III (CTAP-III) is an 85-residue peptide which has been purified from platelets and shown to possess mitogenic activity toward a variety of fibroblastic cell lines. beta-Thromboglobulin (beta TG) is an 81-residue peptide which is derived from CTAP-III by cleavage of the N-terminal tetrapeptide Asn-Leu-Ala-Lys which results in the loss of mitogenic activity. The near-UV CD spectra for the two proteins indicated that the conformations as well as the electronic environments of the two disulfide bonds, and also of the single aromatic tyrosine residue, were similar in CTAP-III and beta TG. However, differences in the far-UV CD spectra of these proteins indicated a substantial decrease in alpha-helical content for beta TG (29%) as compared to CTAP-III (38%). Structure prediction analysis also suggested that the longer N-terminal segment of CTAP-III may form an alpha-helix. The N-terminal region of beta TG, which lacks this tetrapeptide, was predicted to be in an unordered, or possibly a turn, conformation. This predicted structural difference appears to be due to the high helix-forming potential of the N-terminal tetrapeptide Asn-Leu-Ala-Lys in CTAP-III. These results suggest a possible structural role for the N-terminal region of CTAP-III in the expression of the biologic activities of this protein. On the basis of these studies, a reasonable hypothesis to account for the difference in mitogenic activity between beta TG and CTAP-III is that the N-terminal region must be helical for receptor binding to occur.
Erickson
J
J
Protein Crystallography Laboratory, Abbott Laboratories, Illinois 60064.
Davis
L E
LE
Castor
C W
CW
Walz
D A
DA
Anderson
B E
BE
D000595:Amino Acid Sequence; D001792:Blood Platelets / Q000378:metabolism; D002942:Circular Dichroism; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism*; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D001620:beta-Thromboglobulin
D010455:Peptides; D001620:beta-Thromboglobulin; C009862:connective tissue-activating peptide