Structure-function studies of the functional and binding epitope of the human 37 kDa laminin receptor precursor protein.
Expression of the 37 kDa laminin receptor precursor protein (37LRP) correlates directly with increased invasiveness and the metastatic potential of tumors. The 37LRP matures to a 67 kDa protein which facilitates the binding of cancer cells to basement membranes. The palindrome peptide sequence LMWWML, corresponding to the 173-178-residue stretch of the human 37LRP sequence, has been identified as the laminin-1-binding site. Peptides from 37LRP of species that contain this palindrome-bind laminin-1 with high affinity. Nuclear magnetic resonance (NMR) conformational studies have been undertaken on a synthetic 15-residue peptide (KGAHSVGLMWWMLAR) containing the palindrome to establish the structural basis of this activity. To further correlate the structural data with laminin-1-binding function, analogous structural studies were conducted for a similar peptide (RGKHSIGLIWYLLAR) lacking the palindrome, originating from 37LRP sequence of Saccharomyces cerevisiae and exhibiting low laminin-1-binding affinity. Finally, in vitro cell invasion assays were performed to investigate the possibility that the laminin-1-binding affinity of the peptides influences their inhibitory activity.
Jaseja
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M
Center for Protease Research, Department of Chemistry and Molecular Biology, North Dakota State University, Fargo, ND 58105, USA. mahesh.jaseja@ndsu.nodak.edu
Mergen
L
L
Gillette
K
K
Forbes
K
K
Sehgal
I
I
Copié
V
V
D000595:Amino Acid Sequence; D001665:Binding Sites; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology; D011487:Protein Conformation; D011498:Protein Precursors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D017474:Receptors, Laminin / Q000737:chemistry* / Q000378:metabolism; D020539:Sequence Analysis, Protein; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D010455:Peptides; D011498:Protein Precursors; D017474:Receptors, Laminin