PDBsum entry 3axa

Cell adhesion

PDB id: 3axa

Contents

Protein chains

97 a.a.

Waters ×12

PDB id:

3axa

Name:

Cell adhesion

Title:

Crystal structure of afadin pdz domain in complex with thE C-terminal peptide from nectin-3

Structure:

Afadin, nectin-3. Chain: a, b. Fragment: pdz domain (unp 1003-1095), c-terminal peptide (unp 544- 549). Synonym: protein af-6. Engineered: yes. Other_details: the fusion protein of afadin (1003-1095) and nectin-3 (544-549)

Source:

Mus musculus. Mouse, mouse. Organism_taxid: 10090. Gene: mllt4, af6. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.78Å R-factor: 0.241 R-free: 0.263

Authors:

Y.Fujiwara,N.Goda,H.Narita,K.Satomura,A.Nakagawa,T.Sakisaka,M.Suzuki, H.Hiroaki

Key ref:

Y.Fujiwara et al. (2015). Crystal structure of afadin PDZ domain-nectin-3 complex shows the structural plasticity of the ligand-binding site. Protein Sci, 24, 376-385. PubMed id: 25534554 DOI: 10.1002/pro.2628

Date:

31-Mar-11 Release date: 25-Apr-12

Protein chains

Q9JLB9  (NECT3_MOUSE) -  Nectin-3 from Mus musculus

Seq: 549 a.a.

Struc: 97 a.a.*

Protein chains

Q9QZQ1  (AFAD_MOUSE) -  Afadin from Mus musculus

Seq: 1820 a.a.

Struc: 97 a.a.*

* PDB and UniProt seqs differ at 91 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1002/pro.2628

Protein Sci 24:376-385 (2015)

PubMed id: 25534554

Crystal structure of afadin PDZ domain-nectin-3 complex shows the structural plasticity of the ligand-binding site.

Y.Fujiwara, N.Goda, T.Tamashiro, H.Narita, K.Satomura, T.Tenno, A.Nakagawa, M.Oda, M.Suzuki, T.Sakisaka, Y.Takai, H.Hiroaki.

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.