View source for 3axa


==Crystal structure of afadin PDZ domain in complex with the C-terminal peptide from nectin-3==
<StructureSection load='3axa' size='340' side='right'caption='[[3axa]], [[Resolution|resolution]] 2.78&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3axa]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3AXA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3AXA FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.78&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3axa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3axa OCA], [https://pdbe.org/3axa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3axa RCSB], [https://www.ebi.ac.uk/pdbsum/3axa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3axa ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/AFAD_MOUSE AFAD_MOUSE] Belongs to an adhesion system, probably together with the E-cadherin-catenin system, which plays a role in the organization of homotypic, interneuronal and heterotypic cell-cell adherens junctions (AJs). Nectin- and actin-filament-binding protein that connects nectin to the actin cytoskeleton. May play a key role in the organization of epithelial structures of the embryonic ectoderm.<ref>PMID:10477764</ref> [https://www.uniprot.org/uniprot/NECT3_MOUSE NECT3_MOUSE] Plays a role in cell-cell adhesion through heterophilic trans-interactions with nectins-like or other nectins, such as trans-interaction with NECTIN2 at Sertoli-spermatid junctions. Trans-interaction with PVR induces activation of CDC42 and RAC small G proteins through common signaling molecules such as SRC and RAP1. Also involved in the formation of cell-cell junctions, including adherens junctions and synapses. Induces endocytosis-mediated down-regulation of PVR from the cell surface, resulting in reduction of cell movement and proliferation. Plays a role in the morphology of the ciliary body.<ref>PMID:10744716</ref> <ref>PMID:11827984</ref> <ref>PMID:12121624</ref> <ref>PMID:12558799</ref> <ref>PMID:16128743</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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-Phi-X-Phi (Phi, 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 beta sheet between beta2 strands. A major structural change compared with the known AFPDZ structures was observed in the alpha2 helix. We found an approximately 2.5 A-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.

Crystal structure of afadin PDZ domain-nectin-3 complex shows the structural plasticity of the ligand-binding site.,Fujiwara Y, Goda N, Tamashiro T, Narita H, Satomura K, Tenno T, Nakagawa A, Oda M, Suzuki M, Sakisaka T, Takai Y, Hiroaki H Protein Sci. 2015 Mar;24(3):376-85. doi: 10.1002/pro.2628. Epub 2015 Jan 13. PMID:25534554<ref>PMID:25534554</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3axa" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Fujiwara Y]]
[[Category: Goda N]]
[[Category: Hiroaki H]]
[[Category: Nakagawa A]]
[[Category: Narita H]]
[[Category: Sakisaka T]]
[[Category: Satomura K]]
[[Category: Suzuki M]]