Both the dimerization and immunochemical properties of E-cadherin EC1 domain depend on Trp(156) residue.
Using site-directed mutagenesis, we show in this paper that the adhesive interface detected in cadherin crystals is unlikely to mediate adhesive interaction between myc- and flag-tagged E-cadherin molecules in human A-431 cells. We also found that a critical residue within this interface, His(233), is part of the epitope for mAb SHE78-7. This epitope was accessible to the antibody in the adhesive E-cadherin dimers, which is consistent with uninvolvement of the site containing His(233) in cell-cell adhesion. However, both the adhesive dimerization and the integrity of the SHE78-7 epitope depended on the same intramolecular interaction between Trp(156) and its hydrophobic pocket. Our data suggest that this interaction may have an important regulatory function in controlling the surface topology of the NH(2)-terminal domain of E-cadherin.
Laur
Oscar Y
OY
Division of Dermatology, Washington University Medical School, St. Louis, Missouri 63110, USA.
Klingelhöfer
Jörg
J
Troyanovsky
Regina B
RB
Troyanovsky
Sergey M
SM
D000595:Amino Acid Sequence; D015820:Cadherins / Q000737:chemistry* / Q000378:metabolism*; D002448:Cell Adhesion; D019281:Dimerization; D000939:Epitopes / Q000737:chemistry; D006639:Histidine / Q000737:chemistry; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014364:Tryptophan / Q000737:chemistry
D015820:Cadherins; D000939:Epitopes; D011994:Recombinant Proteins; D006639:Histidine; D014364:Tryptophan