Cell-Cell Communication

Cadherin-mediated Cell-Cell Adhesion

Cell-cell interactions are one of the fundamental functions of eukaryotic cells.  Cadherin is a calcium-dependent cell-cell adhesion molecule and acts as a morphoreguratory factor.  Our goal is to understand how cadherins can mediate cell-cell interactions and maintain a stable formation of tissues.  We have determined the solution structure of the E-cadherin first repeat (1SUH), and the crystal structure of the first and second repeat (1EDH) in collaboration with Dr. J. Rini.  We also would like to understand how the loss of the cadherin function can contribute to cancer metastasis and the development of certain types of tumour.

Nagar, B., Overduin, M., Ikura, M. and Rini, J. (1996)  Structural Basis of Calcium Induced E-Cadherin Rigidification and Dimerization.  Nature, 380, 360-364.

Overduin, M., Harvey, T.S., Bagby, S., Tong, K.I., Yau, P., Takeichi, M. and Ikura, M. (1995) Solution Structure of the Epithelial Cadherin Domain Responsible for Selective Cell Adhesion. Science 267, 386-389.

Cell-cell Interaction by Protein S

Gram-negative bacterium Myxococcus xanthus undergoes a unique cell cycle, during which it forms a multicellular structure called a fruiting body, a process which requires calcium ions. Protein S is a development-specific calcium-binding protein which is implicated in the cell-cell interaction process in this bacterium.  We have determined the structure of calcium-bound protein S (1PRR) by NMR in collaboration with Dr. S. Inouye, and are currently using this protein for the study of protein folding in collaboration with Dr. Avi Chakrabartty.

Bagby, S., Harvey, T.S., Eagle, S.G., Inouye, S. and Ikura, M. (1994)  NMR-Derived Three-Dimensional Solution Structure of Protein S Complexes with Calcium.  Structure 2, 107-122.

Bagby, S., Harvey, T.S., Eagle, S.G., Inouye, S. and Ikura, M. (1994)  Structural Similarity of a Developmentally Regulated Bacterial Spore Coat Protein to Gamma-crystallins of the Vertebrate Eye Lens.  Proc. Natl. Acad. Sci. U.S.A. 91, 4308-4312.