6ARQ

Crystal structure of CD96 (D1) bound to CD155/necl-5 (D1-3)

Summary for 6ARQ

• Entry DOI: 10.2210/pdb6arq/pdb
• Descriptor: T-cell surface protein tactile, Poliovirus receptor, alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: natural killer cell receptor, adhesion molecule, immunoglobulin fold, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 51175.27

Authors

Deuss, F.A.,Watson, G.M.,Rossjohn, J.,Berry, R. (deposition date: 2017-08-23, release date: 2018-11-21, Last modification date: 2024-10-23)

Primary citation

Deuss, F.A.,Watson, G.M.,Fu, Z.,Rossjohn, J.,Berry, R.
Structural Basis for CD96 Immune Receptor Recognition of Nectin-like Protein-5, CD155.
Structure, 27:219-228.e3, 2019

PubMed Abstract: CD96, DNAM-1, and TIGIT constitute a group of immunoglobulin superfamily receptors that are key regulators of tumor immune surveillance. Within this axis, CD96 recognizes the adhesion molecule nectin-like protein-5 (necl-5), although the molecular basis underpinning this interaction remains unclear. We show that the first immunoglobulin domain (D1) of CD96 is sufficient to mediate a robust interaction with necl-5, but not the DNAM-1 and TIGIT ligand, nectin-2. The crystal structure of CD96-D1 bound to the necl-5 ectodomain revealed that CD96 recognized necl-5 D1 via a conserved "lock-and-key" interaction observed across TIGIT:necl complexes. Specific necl-5 recognition was underpinned by a novel structural motif within CD96, namely an "ancillary key". Mutational analysis showed that this specific residue was critical for necl-5 binding, while simultaneously providing insights into the unique ligand specificity of CD96.

PubMed: 30528596
DOI: 10.1016/j.str.2018.10.023

Experimental method

X-RAY DIFFRACTION (2.88 Å)