3axa

From Proteopedia

(Difference between revisions)

Current revision

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

Structural highlights

3axa is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.78Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] 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.^[2] ^[3] ^[4] ^[5] ^[6]

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^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ikeda W, Nakanishi H, Miyoshi J, Mandai K, Ishizaki H, Tanaka M, Togawa A, Takahashi K, Nishioka H, Yoshida H, Mizoguchi A, Nishikawa S, Takai Y. Afadin: A key molecule essential for structural organization of cell-cell junctions of polarized epithelia during embryogenesis. J Cell Biol. 1999 Sep 6;146(5):1117-32. PMID:10477764
↑ Satoh-Horikawa K, Nakanishi H, Takahashi K, Miyahara M, Nishimura M, Tachibana K, Mizoguchi A, Takai Y. Nectin-3, a new member of immunoglobulin-like cell adhesion molecules that shows homophilic and heterophilic cell-cell adhesion activities. J Biol Chem. 2000 Apr 7;275(14):10291-9. PMID:10744716
↑ Mizoguchi A, Nakanishi H, Kimura K, Matsubara K, Ozaki-Kuroda K, Katata T, Honda T, Kiyohara Y, Heo K, Higashi M, Tsutsumi T, Sonoda S, Ide C, Takai Y. Nectin: an adhesion molecule involved in formation of synapses. J Cell Biol. 2002 Feb 4;156(3):555-65. Epub 2002 Feb 4. PMID:11827984 doi:http://dx.doi.org/10.1083/jcb.200103113
↑ Ozaki-Kuroda K, Nakanishi H, Ohta H, Tanaka H, Kurihara H, Mueller S, Irie K, Ikeda W, Sakai T, Wimmer E, Nishimune Y, Takai Y. Nectin couples cell-cell adhesion and the actin scaffold at heterotypic testicular junctions. Curr Biol. 2002 Jul 9;12(13):1145-50. PMID:12121624
↑ Honda T, Shimizu K, Kawakatsu T, Yasumi M, Shingai T, Fukuhara A, Ozaki-Kuroda K, Irie K, Nakanishi H, Takai Y. Antagonistic and agonistic effects of an extracellular fragment of nectin on formation of E-cadherin-based cell-cell adhesion. Genes Cells. 2003 Jan;8(1):51-63. PMID:12558799
↑ Sato T, Irie K, Okamoto R, Ooshio T, Fujita N, Takai Y. Common signaling pathway is used by the trans-interaction of Necl-5/Tage4/PVR/CD155 and nectin, and of nectin and nectin during the formation of cell-cell adhesion. Cancer Sci. 2005 Sep;96(9):578-89. PMID:16128743 doi:http://dx.doi.org/CAS087
↑ 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. 2015 Mar;24(3):376-85. doi: 10.1002/pro.2628. Epub 2015 Jan 13. PMID:25534554 doi:http://dx.doi.org/10.1002/pro.2628

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3axa"

@@ Line 1: / Line 1: @@
-[[Image:3axa.jpg|left|200px]]
-<!--
+==Crystal structure of afadin PDZ domain in complex with the C-terminal peptide from nectin-3==
-The line below this paragraph, containing "STRUCTURE_3axa", creates the "Structure Box" on the page.
+<StructureSection load='3axa' size='340' side='right'caption='[[3axa]], [[Resolution|resolution]] 2.78&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<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>
-or leave the SCENE parameter empty for the default display.
+</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>
-{{STRUCTURE_3axa|  PDB=3axa  |  SCENE=  }}
+</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 in complex with the C-terminal peptide from nectin-3===
+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>
-==About this Structure==
+</div>
-[[3axa]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus,_mus_musculus Mus musculus, mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3AXA OCA].
+<div class="pdbe-citations 3axa" style="background-color:#fffaf0;"></div>
-[[Category: Mus musculus, mus musculus]]
+== References ==
-[[Category: Fujiwara, Y.]]
+<references/>
-[[Category: Goda, N.]]
+__TOC__
-[[Category: Hiroaki, H.]]
+</StructureSection>
-[[Category: Nakagawa, A.]]
+[[Category: Large Structures]]
-[[Category: Narita, H.]]
+[[Category: Mus musculus]]
-[[Category: Sakisaka, T.]]
+[[Category: Fujiwara Y]]
-[[Category: Satomura, K.]]
+[[Category: Goda N]]
-[[Category: Suzuki, M.]]
+[[Category: Hiroaki H]]
-[[Category: Af-6]]
+[[Category: Nakagawa A]]
-[[Category: Cell adhesion]]
+[[Category: Narita H]]
-[[Category: Fusion protein]]
+[[Category: Sakisaka T]]
-[[Category: Pdz domain]]
+[[Category: Satomura K]]
+[[Category: Suzuki M]]

3axa

From Proteopedia

Current revision

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

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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