3AXA

Crystal structure of afadin PDZ domain in complex with the C-terminal peptide from nectin-3

Summary for 3AXA

• Entry DOI: 10.2210/pdb3axa/pdb
• Descriptor: Afadin, Nectin-3 (2 entities in total)
• Functional Keywords: pdz domain, af-6, fusion protein, cell adhesion
• Biological source: Mus musculus (mouse, mouse); More
• Cellular location: Cell membrane ; Single-pass membrane protein : Q9JLB9
• Total number of polymer chains: 2
• Total formula weight: 22209.42

Authors

Fujiwara, Y.,Goda, N.,Narita, H.,Satomura, K.,Nakagawa, A.,Sakisaka, T.,Suzuki, M.,Hiroaki, H. (deposition date: 2011-03-31, release date: 2012-04-25, Last modification date: 2023-11-01)

Primary citation

Fujiwara, Y.,Goda, N.,Tamashiro, T.,Narita, H.,Satomura, K.,Tenno, T.,Nakagawa, A.,Oda, M.,Suzuki, M.,Sakisaka, T.,Takai, Y.,Hiroaki, H.
Crystal structure of afadin PDZ domain-nectin-3 complex shows the structural plasticity of the ligand-binding site.
Protein Sci., 24:376-385, 2015

PubMed 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.

PubMed: 25534554
DOI: 10.1002/pro.2628

Experimental method

X-RAY DIFFRACTION (2.78 Å)