5ZO2

Crystal structure of mouse nectin-like molecule 4 (mNecl-4) full ectodomain in complex with mouse nectin-like molecule 1 (mNecl-1) Ig1 domain, 3.3A

Summary for 5ZO2

• Entry DOI: 10.2210/pdb5zo2/pdb
• Related: 1Z9M 5ZO1
• Descriptor: Cell adhesion molecule 4, Cell adhesion molecule 3, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: cell adhesion molecule, glycoprotein, ig domain, syncam, cadm, nectin-like, necl-4, necl-1, axon, schwann cell, molecular replacement, myelogenesis, heterogeneous dimer, cell adhesion
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 3
• Total formula weight: 83175.59

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: 2023-11-22)

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 (3.29 Å)