4H5S

Complex structure of Necl-2 and CRTAM

Summary for 4H5S

• Entry DOI: 10.2210/pdb4h5s/pdb
• Descriptor: Cytotoxic and regulatory T-cell molecule, Cell adhesion molecule 1 (3 entities in total)
• Functional Keywords: ig fold, cell adhesion, immune recognition
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein (Potential): O95727; Cell membrane; Single-pass type I membrane protein: Q9BY67
• Total number of polymer chains: 2
• Total formula weight: 22874.85

Authors

Zhang, S.,Lu, G.,Qi, J.,Li, Y.,Zhang, Z.,Zhang, B.,Yan, J.,Gao, G.F. (deposition date: 2012-09-18, release date: 2013-08-07, Last modification date: 2022-08-24)

Primary citation

Zhang, S.,Lu, G.,Qi, J.,Li, Y.,Zhang, Z.,Zhang, B.,Fan, Z.,Yan, J.,Gao, G.F.
Competition of cell adhesion and immune recognition: insights into the interaction between CRTAM and nectin-like 2.
Structure, 21:1430-1439, 2013

PubMed Abstract: Nectin and nectin-like proteins are cell adhesion molecules that mediate the formation of cell adherens junctions by forming homo- or heterodimers. Some members of this protein family can also be used by immune receptors to mediate immune recognition. For instance, nectin-like 2 (Necl-2) is used as a ligand for the immune system by interaction with the immune receptor CRTAM (class-I MHC-restricted T cell associated molecule), which is mainly expressed on the surface of cytotoxic lymphocyte cells. However, the Necl-2/CRTAM binding mode and its relationship to cell adhesion are not known. Here, we report a Necl-2/CRTAM complex structure, demonstrating that Necl-2 binding to CRTAM competes with the dimerization of CRTAM and possibly Necl-2. Necl-2 occupies the CRTAM homodimer interface, making homodimerization impossible. Mutational and functional analyses identified key amino acids (double "lock-and-key") responsible for the binding. Our work illustrates how the cell adhesion molecule Necl-2 competitively binds the immune receptor CRTAM.

PubMed: 23871486
DOI: 10.1016/j.str.2013.06.006

Experimental method

X-RAY DIFFRACTION (1.7 Å)