Dimerization mechanism and structural features of human LI-cadherin [article]

Anna Yui, Jose M. M. Caaveiro, Daisuke Kuroda, Makoto Nakakido, Satoru Nagatoishi, Shuichiro Goda, Takahiro Maruno, Susumu Uchiyama, Kouhei Tsumoto
2020 bioRxiv   pre-print
LI-cadherin is a member of cadherin superfamily which is a Ca2+-dependent cell adhesion protein. Its expression is observed on various types of cells in the human body such as normal small intestine and colon cells, and gastric cancer cells. Because its expression is not observed on normal gastric cells, LI-cadherin is a promising target for gastric cancer imaging. However, since the cell adhesion mechanism of LI-cadherin has remained unknown, rational design of therapeutic molecules targeting
more » ... olecules targeting this cadherin has been complicated. Here, we have studied the homodimerization mechanism of LI-cadherin. We report the crystal structure of the LI-cadherin EC1-4 homodimer. The EC1-4 homodimer exhibited a unique architecture different from that of other cadherins reported so far. The crystal structure also revealed that LI-cadherin possesses a noncanonical calcium ion-free linker between EC2 and EC3. Various biochemical techniques and molecular dynamics (MD) simulations were employed to elucidate the mechanism of homodimerization. We also showed that the formation of the homodimer observed by the crystal structure is necessary for LI-cadherin-dependent cell adhesion by performing cell aggregation assay.
doi:10.1101/2020.09.18.291195 fatcat:txljjmgvtzc73gwbtppa6goqu4