7CYM

Crystal structure of LI-Cadherin EC1-4

Summary for 7CYM

• Entry DOI: 10.2210/pdb7cym/pdb
• Descriptor: Cadherin-17, alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: li-cadherin, dimerization, md simulations, saxs, cell-adhesion, analytical ultracentrifugation, protein chemistry, cell adhesion
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 102815.65

Authors

Caaveiro, J.M.M.,Yui, A.,Tsumoto, K. (deposition date: 2020-09-03, release date: 2021-08-18, Last modification date: 2023-11-29)

Primary citation

Yui, A.,Caaveiro, J.M.M.,Kuroda, D.,Nakakido, M.,Nagatoishi, S.,Goda, S.,Maruno, T.,Uchiyama, S.,Tsumoto, K.
Mechanism of dimerization and structural features of human LI-cadherin.
J.Biol.Chem., 297:101054-101054, 2021

PubMed Abstract: Liver intestine (LI)-cadherin is a member of the cadherin superfamily, which encompasses a group of Ca-dependent cell-adhesion proteins. The expression of LI-cadherin 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, because the cell adhesion mechanism of LI-cadherin has remained unknown, rational design of therapeutic molecules targeting this cadherin has been hampered. Here, we have studied the homodimerization mechanism of LI-cadherin. We report the crystal structure of the LI-cadherin homodimer containing its first four extracellular cadherin repeats (EC1-4). The EC1-4 homodimer exhibited a unique architecture different from that of other cadherins reported so far, driven by the interactions between EC2 of one protein chain and EC4 of the second protein chain. The crystal structure also revealed that LI-cadherin possesses a noncanonical calcium ion-free linker between the EC2 and EC3 domains. Various biochemical techniques and molecular dynamics simulations were employed to elucidate the mechanism of homodimerization. We also showed that the formation of the homodimer observed in the crystal structure is necessary for LI-cadherin-dependent cell adhesion by performing cell aggregation assays. Taken together, our data provide structural insights necessary to advance the use of LI-cadherin as a target for imaging gastric cancer.

PubMed: 34364873
DOI: 10.1016/j.jbc.2021.101054

Experimental method

X-RAY DIFFRACTION (2.7 Å)