title: Structure-function studies of the functional and binding epitope of the human 37 kDa laminin receptor precursor protein.
abstract: 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.
authors.affiliation: Center for Protease Research, Department of Chemistry and Molecular Biology, North Dakota State University, Fargo, ND 58105, USA. mahesh.jaseja@ndsu.nodak.edu
authors.forename: M
authors.initials: M
authors.lastname: Jaseja
authors.forename: L
authors.initials: L
authors.lastname: Mergen
authors.forename: K
authors.initials: K
authors.lastname: Gillette
authors.forename: K
authors.initials: K
authors.lastname: Forbes
authors.forename: I
authors.initials: I
authors.lastname: Sehgal
authors.forename: V
authors.initials: V
authors.lastname: Copié
mesh_terms: 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
chemical_list: D010455:Peptides; D011498:Protein Precursors; D017474:Receptors, Laminin