Peptide ligands for the fibronectin type II modules of matrix metalloproteinase 2 (MMP-2).
The interaction of matrix metalloproteinase 2 (MMP-2) with gelatin is mediated by three repeats homologous to fibronectin type II (FN2) modules, which are inserted in the catalytic domain in proximity of the active site. We screened a random 15-mer phage display library to identify peptides that interact with the FN2 modules of MMP-2. Interestingly, the selected peptides are not gelatin-like and do not share a common, obvious sequence motif. However, they contain a high proportion of aromatic residues. The interactions of two peptides, WHWRH0RIPLQLAAGR and THSHQWRHHQFPAPT, with constructs comprising the in-tandem first and second and second and third FN2 modules of MMP-2 (Col-12 and Col-23, respectively) were characterized by NMR. Both peptides interact with Col-12 and Col-23 with apparent association constants in the mm(-1) range. Peptide binding results in perturbation of signals from residues located in the gelatin-binding pocket and flexible parts of the molecule. Although the former finding suggests that the gelatin-binding site is involved in the contact, the interpretation of the latter is less straightforward and may well reflect both the direct and indirect effects of the interaction.
Trexler
Maria
M
Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, Budapest H-1518, Hungary.
Briknarová
Klára
K
Gehrmann
Marion
M
Llinás
Miguel
M
Patthy
László
L
D000595:Amino Acid Sequence; D001665:Binding Sites; D003094:Collagen / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D019151:Peptide Library; D017434:Protein Structure, Tertiary
D005353:Fibronectins; D008024:Ligands; D010446:Peptide Fragments; D019151:Peptide Library; D003094:Collagen; D020778:Matrix Metalloproteinase 2