5ZO1

Crystal structure of mouse nectin-like molecule 4 (mNecl-4) full ectodomain (Ig1-Ig3), 2.2A

Summary for 5ZO1

• Entry DOI: 10.2210/pdb5zo1/pdb
• Related: 1Z9M
• Descriptor: Cell adhesion molecule 4, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, GLYCEROL, ... (4 entities in total)
• Functional Keywords: cell adhesion molecule, glycoprotein, ig-like domain, necl4, necl, nectin, nectin-like molecules, cadm, native-sad, disulfide bridges, syncam4, schwann cell, myelogenesis, cell adhesion
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 1
• Total formula weight: 34057.88

Authors

Liu, X.,An, T.,Li, D.,Fan, Z.,Xiang, P.,Li, C.,Ju, W.,Li, J.,Hu, G.,Qin, B.,Yin, B.,Wojdyla, J.A.,Wang, M.,Yuan, J.,Qiang, B.,Shu, P.,Cui, S.,Peng, X. (deposition date: 2018-04-12, release date: 2019-01-30, Last modification date: 2024-11-06)

Primary citation

Liu, X.,An, T.,Li, D.,Fan, Z.,Xiang, P.,Li, C.,Ju, W.,Li, J.,Hu, G.,Qin, B.,Yin, B.,Wojdyla, J.A.,Wang, M.,Yuan, J.,Qiang, B.,Shu, P.,Cui, S.,Peng, X.
Structure of the heterophilic interaction between the nectin-like 4 and nectin-like 1 molecules.
Proc. Natl. Acad. Sci. U.S.A., 116:2068-2077, 2019

PubMed Abstract: Nectin-like (Necl) molecules are Ca-independent Ig-like transmembrane cell adhesion molecules that participate in junctions between different cell types. The specific cell-cell adhesions mediated by Necl proteins are important in neural development and have been implicated in neurodegenerative diseases. Here, we present the crystal structure of the mouse Necl-4 full ectodomain and the structure of the heterophilic Necl ectodomain complex formed by the mNecl-4 and mNecl-1 ectodomains. We demonstrate that, while the ectodomain of mNecl-4 is monomeric, it forms a stable heterodimer with Ig1 of mNecl-1, with an affinity significantly higher than that observed for self-dimerization of the mNecl-1 ectodomain. We validated our structural characterizations by performing a surface plasmon resonance assay and an Fc fusion protein binding assay in mouse primary dorsal root ganglia neurites and Schwann cells and identified a selection of residues important for heterophilic interactions. Finally, we proposed a model of Necl binding specificity that involves an induced-fit conformational change at the dimerization interface.

PubMed: 30674679
DOI: 10.1073/pnas.1810969116

Experimental method

X-RAY DIFFRACTION (2.201 Å)