7ev1 | pdb_00007ev1
Crystal structure of LI-Cadherin EC1-2
Structural highlights
FunctionCAD17_HUMAN Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. LI-cadherin may have a role in the morphological organization of liver and intestine. Involved in intestinal peptide transport.[1] Publication Abstract from PubMedLI-cadherin is a member of the cadherin superfamily, which encompasses a group of Ca(2+)-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, since 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 other 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 (MD) 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 insight necessary to advance the use of LI-cadherin as a target for imaging gastric cancer. Mechanism of dimerization and structural features of human LI-cadherin.,Yui A, Caaveiro JMM, Kuroda D, Nakakido M, Nagatoishi S, Goda S, Maruno T, Uchiyama S, Tsumoto K J Biol Chem. 2021 Aug 5:101054. doi: 10.1016/j.jbc.2021.101054. PMID:34364873[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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