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| | ==Complex of GID4 fragment with short peptide== | | ==Complex of GID4 fragment with short peptide== |
| - | <StructureSection load='6cd8' size='340' side='right' caption='[[6cd8]], [[Resolution|resolution]] 1.60Å' scene=''> | + | <StructureSection load='6cd8' size='340' side='right'caption='[[6cd8]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6cd8]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CD8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CD8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6cd8]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CD8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CD8 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></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]] 1.6Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GID4, C17orf39, VID24 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></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=6cd8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cd8 OCA], [http://pdbe.org/6cd8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cd8 RCSB], [http://www.ebi.ac.uk/pdbsum/6cd8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cd8 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=6cd8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cd8 OCA], [https://pdbe.org/6cd8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cd8 RCSB], [https://www.ebi.ac.uk/pdbsum/6cd8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cd8 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/GID4_HUMAN GID4_HUMAN] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Arrowsmith, C H]] | + | [[Category: Large Structures]] |
| - | [[Category: Bountra, C]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Dong, C]] | + | [[Category: Arrowsmith CH]] |
| - | [[Category: Edwards, A M]] | + | [[Category: Bountra C]] |
| - | [[Category: Min, J]] | + | [[Category: Dong C]] |
| - | [[Category: Structural genomic]] | + | [[Category: Edwards AM]] |
| - | [[Category: Tempel, W]] | + | [[Category: Min J]] |
| - | [[Category: Peptide binding protein]] | + | [[Category: Tempel W]] |
| - | [[Category: Sgc]]
| + | |
| Structural highlights
Function
GID4_HUMAN
Publication Abstract from PubMed
The N-end rule pathway senses the N-terminal destabilizing residues of degradation substrates for the ubiquitin-proteasome system, whose integrity shields against various human syndromes including cancer and cardiovascular diseases. GID4, a subunit of the ubiquitin ligase GID complex, has been recently identified as the N-recognin of the new branch of the N-end rule pathway responsible for recognizing substrates bearing N-terminal proline residues (Pro/N-degrons). However, the molecular mechanism of GID4-mediated Pro/N-degron recognition remains largely unexplored. Here, we report the first crystal structures of human GID4 alone and in complex with various Pro/N-degrons. Our complex crystal structures, together with biophysical analyses, delineate the GID4-mediated Pro/N-degron recognition mechanism and substrate selection criteria for the Pro/N-end rule pathway. These mechanistic data on the Pro/N-recognin activity of GID4 will serve as a foundation to facilitate the identification of authentic physiological substrates as well as the development of inhibitors of therapeutic values for the Pro/N-end rule pathway.
Molecular basis of GID4-mediated recognition of degrons for the Pro/N-end rule pathway.,Dong C, Zhang H, Li L, Tempel W, Loppnau P, Min J Nat Chem Biol. 2018 May;14(5):466-473. doi: 10.1038/s41589-018-0036-1. Epub 2018 , Apr 9. PMID:29632410[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dong C, Zhang H, Li L, Tempel W, Loppnau P, Min J. Molecular basis of GID4-mediated recognition of degrons for the Pro/N-end rule pathway. Nat Chem Biol. 2018 May;14(5):466-473. doi: 10.1038/s41589-018-0036-1. Epub 2018 , Apr 9. PMID:29632410 doi:http://dx.doi.org/10.1038/s41589-018-0036-1
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