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| | <StructureSection load='5zys' size='340' side='right'caption='[[5zys]], [[Resolution|resolution]] 1.78Å' scene=''> | | <StructureSection load='5zys' size='340' side='right'caption='[[5zys]], [[Resolution|resolution]] 1.78Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5zys]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZYS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZYS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5zys]] 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=5ZYS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZYS FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Magi1, Baiap1, Bap1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.78Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5zys FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zys OCA], [http://pdbe.org/5zys PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zys RCSB], [http://www.ebi.ac.uk/pdbsum/5zys PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zys ProSAT]</span></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=5zys FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zys OCA], [https://pdbe.org/5zys PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zys RCSB], [https://www.ebi.ac.uk/pdbsum/5zys PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zys ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MAGI1_MOUSE MAGI1_MOUSE]] May play a role as scaffolding protein at cell-cell junctions. May regulate acid-induced ASIC3 currents by modulating its expression at the cell surface.<ref>PMID:15317815</ref> | + | [https://www.uniprot.org/uniprot/MAGI1_MOUSE MAGI1_MOUSE] May play a role as scaffolding protein at cell-cell junctions. May regulate acid-induced ASIC3 currents by modulating its expression at the cell surface.<ref>PMID:15317815</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | BACKGROUND: The slit diaphragm is a specialized adhesion junction between opposing podocytes, establishing the final filtration barrier that prevents passage of proteins from the capillary lumen into the urinary space. Nephrin, the key structural and signaling adhesion molecule expressed in the slit diaphragm, contains an evolutionally conserved, atypical PDZ-binding motif (PBM) reported to bind to a variety of proteins in the slit diaphragm. Several mutations in NPHS1 (the gene encoding nephrin) that result in nephrin lacking an intact PBM are associated with glomerular diseases. However, the molecular basis of nephrin-PBM-mediated protein complexes is still unclear. METHODS: Using a combination of biochemic, biophysic, and cell biologic approaches, we systematically investigated the interactions between nephrin-PBM and PDZ domain-containing proteins in the slit diaphragm. RESULTS: We found that nephrin-PBM specifically binds to one member of the membrane-associated guanylate kinase family of scaffolding proteins, MAGI1, but not to another, MAGI2. The complex structure of MAGI1-PDZ3/nephrin-PBM reveals that the Gly at the -3 position of nephrin-PBM is the determining feature for MAGI1-PDZ3 recognition, which sharply contrasts with the typical PDZ/PBM binding mode. A single gain-of-function mutation within MAGI2 enabled nephrin-PBM binding. In addition, using our structural analysis, we developed a highly efficient inhibitory peptide capable of specifically blocking the nephrin/MAGI1 interaction. CONCLUSIONS: MAGI1 interacts with nephrin-PBM with exquisite specificity. A newly developed, potent inhibitory peptide that blocks this interaction may be useful for future functional investigations in vivo. Our findings also provide possible explanations for the diseases caused by NPHS1 mutations.
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| - | Structural Basis of Highly Specific Interaction between Nephrin and MAGI1 in Slit Diaphragm Assembly and Signaling.,Weng Z, Shang Y, Ji Z, Ye F, Lin L, Zhang R, Zhu J J Am Soc Nephrol. 2018 Sep;29(9):2362-2371. doi: 10.1681/ASN.2017121275. Epub, 2018 Jul 13. PMID:30006415<ref>PMID:30006415</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 5zys" style="background-color:#fffaf0;"></div>
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| | ==See Also== | | ==See Also== |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Shng, Y]] | + | [[Category: Shng Y]] |
| - | [[Category: Weng, Z F]] | + | [[Category: Weng ZF]] |
| - | [[Category: Zhang, R G]] | + | [[Category: Zhang RG]] |
| - | [[Category: Zhu, J W]] | + | [[Category: Zhu JW]] |
| - | [[Category: Cell adhesion]]
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| - | [[Category: Magi1- nephrin complex]]
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| - | [[Category: Nephrotic syndrome]]
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| - | [[Category: Slit diaphragm]]
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