PDBsum entry 3axa

Cell adhesion

PDB id: 3axa

Contents

Protein chains

97 a.a.

Waters ×12

References listed in PDB file

Key reference

• Title: Crystal structure of afadin pdz domain-Nectin-3 complex shows the structural plasticity of the ligand-Binding site.
• Authors: Y.Fujiwara, N.Goda, T.Tamashiro, H.Narita, K.Satomura, T.Tenno, A.Nakagawa, M.Oda, M.Suzuki, T.Sakisaka, Y.Takai, H.Hiroaki.
• Ref.: Protein Sci, 2015, 24, 376-385. [DOI no: 10.1002/pro.2628]
• PubMed id: 25534554

Abstract

Afadin, a scaffold protein localized in adherens junctions (AJs), links nectins to the actin cytoskeleton. Nectins are the major cell adhesion molecules of AJs. At the initial stage of cell-cell junction formation, the nectin-afadin interaction plays an indispensable role in AJ biogenesis via recruiting and tethering other components. The afadin PDZ domain (AFPDZ) is responsible for binding the cytoplasmic C-terminus of nectins. AFPDZ is a class II PDZ domain member, which prefers ligands containing a class II PDZ-binding motif, X-Φ-X-Φ (Φ, hydrophobic residues); both nectins and other physiological AFPDZ targets contain this class II motif. Here, we report the first crystal structure of the AFPDZ in complex with the nectin-3 C-terminal peptide containing the class II motif. We engineered the nectin-3 C-terminal peptide and AFPDZ to produce an AFPDZ-nectin-3 fusion protein and succeeded in obtaining crystals of this complex as a dimer. This novel dimer interface was created by forming an antiparallel β sheet between β2 strands. A major structural change compared with the known AFPDZ structures was observed in the α2 helix. We found an approximately 2.5 Å-wider ligand-binding groove, which allows the PDZ to accept bulky class II ligands. Apparently, the last three amino acids of the nectin-3 C-terminus were sufficient to bind AFPDZ, in which the two hydrophobic residues are important.