Identification of the anti-adhesive site buried within the heparin-binding domain of fibronectin.
We recently found that heparin-binding domain 2 (Hep 2) of fibronectin (FN) exhibits cryptic anti-adhesive activity. In order to locate the anti-adhesive site, a number of synthetic peptides which represents the primary structure of the Hep 2 domain were characterized as to their ability to decrease the adhesion of A375SM melanoma cells to FN substrate. Only one peptide (T-E-A-T-I-T-G-L-E-P-G-T-E-Y-T-I-Y-V-I-A-L, residues 1835-1855) (peptide III14-2), which is situated between the previously identified adhesive sites, FN-C/H-I and II, decreased the cell adhesion to FN. Assaying of the anti-adhesive activities of sub-peptides showed that the hydrophobic moiety of peptide III14-2 (underlined sequence) seems to be indispensable for the anti-adhesive activity. These results suggest that anti-adhesive activity is closely associated with the sequence, Y-T-I-V-I-A-L, that is usually buried within the Hep 2 domain structure because of its hydrophobic nature.
Fukai
F
F
Department of Patho-Physiology, Faculty of Pharmaceutical Sciences, Science University of Tokyo. fukai@ps.kagu.sut.ac.jp
Hasebe
S
S
Ueki
M
M
Mutoh
M
M
Ohgi
C
C
Takahashi
H
H
Takeda
K
K
Katayama
T
T
D000595:Amino Acid Sequence; D001665:Binding Sites; D002448:Cell Adhesion; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000737:chemistry / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000378:metabolism; D010449:Peptide Mapping
D005353:Fibronectins; D010446:Peptide Fragments; D006493:Heparin