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| | <StructureSection load='6zmm' size='340' side='right'caption='[[6zmm]], [[Resolution|resolution]] 2.96Å' scene=''> | | <StructureSection load='6zmm' size='340' side='right'caption='[[6zmm]], [[Resolution|resolution]] 2.96Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6zmm]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZMM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZMM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6zmm]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZMM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZMM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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]] 2.96Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NDRG1, CAP43, DRG1, RTP ([https://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=CL:CHLORIDE+ION'>CL</scene></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=6zmm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zmm OCA], [https://pdbe.org/6zmm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zmm RCSB], [https://www.ebi.ac.uk/pdbsum/6zmm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zmm 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=6zmm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zmm OCA], [https://pdbe.org/6zmm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zmm RCSB], [https://www.ebi.ac.uk/pdbsum/6zmm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zmm ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/NDRG1_HUMAN NDRG1_HUMAN]] Charcot-Marie-Tooth disease type 4D. The disease is caused by variants affecting the gene represented in this entry.
| + | [https://www.uniprot.org/uniprot/NDRG1_HUMAN NDRG1_HUMAN] Charcot-Marie-Tooth disease type 4D. The disease is caused by variants affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/NDRG1_HUMAN NDRG1_HUMAN]] Stress-responsive protein involved in hormone responses, cell growth, and differentiation. Acts as a tumor suppressor in many cell types. Necessary but not sufficient for p53/TP53-mediated caspase activation and apoptosis. Has a role in cell trafficking, notably of the Schwann cell, and is necessary for the maintenance and development of the peripheral nerve myelin sheath. Required for vesicular recycling of CDH1 and TF. May also function in lipid trafficking. Protects cells from spindle disruption damage. Functions in p53/TP53-dependent mitotic spindle checkpoint. Regulates microtubule dynamics and maintains euploidy.<ref>PMID:15247272</ref> <ref>PMID:15377670</ref> <ref>PMID:17786215</ref> <ref>PMID:9766676</ref>
| + | [https://www.uniprot.org/uniprot/NDRG1_HUMAN NDRG1_HUMAN] Stress-responsive protein involved in hormone responses, cell growth, and differentiation. Acts as a tumor suppressor in many cell types. Necessary but not sufficient for p53/TP53-mediated caspase activation and apoptosis. Has a role in cell trafficking, notably of the Schwann cell, and is necessary for the maintenance and development of the peripheral nerve myelin sheath. Required for vesicular recycling of CDH1 and TF. May also function in lipid trafficking. Protects cells from spindle disruption damage. Functions in p53/TP53-dependent mitotic spindle checkpoint. Regulates microtubule dynamics and maintains euploidy.<ref>PMID:15247272</ref> <ref>PMID:15377670</ref> <ref>PMID:17786215</ref> <ref>PMID:9766676</ref> |
| | <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: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Kursula, P]] | + | [[Category: Kursula P]] |
| - | [[Category: Mustonen, V]] | + | [[Category: Mustonen V]] |
| - | [[Category: Ruskamo, S]] | + | [[Category: Ruskamo S]] |
| - | [[Category: Lipid binding protein]]
| + | |
| - | [[Category: Metal binding protein]]
| + | |
| - | [[Category: Tumor suppressor]]
| + | |
| Structural highlights
Disease
NDRG1_HUMAN Charcot-Marie-Tooth disease type 4D. The disease is caused by variants affecting the gene represented in this entry.
Function
NDRG1_HUMAN Stress-responsive protein involved in hormone responses, cell growth, and differentiation. Acts as a tumor suppressor in many cell types. Necessary but not sufficient for p53/TP53-mediated caspase activation and apoptosis. Has a role in cell trafficking, notably of the Schwann cell, and is necessary for the maintenance and development of the peripheral nerve myelin sheath. Required for vesicular recycling of CDH1 and TF. May also function in lipid trafficking. Protects cells from spindle disruption damage. Functions in p53/TP53-dependent mitotic spindle checkpoint. Regulates microtubule dynamics and maintains euploidy.[1] [2] [3] [4]
Publication Abstract from PubMed
N-myc downstream regulated gene 1 (NDRG1) is a tumour suppressor involved in vesicular trafficking and stress response. NDRG1 participates in peripheral nerve myelination, and mutations in the NDRG1 gene lead to Charcot-Marie-Tooth neuropathy. The 43-kDa NDRG1 is considered as an inactive member of the alpha/beta hydrolase superfamily. In addition to a central alpha/beta hydrolase fold domain, NDRG1 consists of a short N terminus and a C-terminal region with three 10-residue repeats. We determined the crystal structure of the alpha/beta hydrolase domain of human NDRG1 and characterised the structure and dynamics of full-length NDRG1. The structure of the alpha/beta hydrolase domain resembles the canonical alpha/beta hydrolase fold with a central beta sheet surrounded by alpha helices. Small-angle X-ray scattering and CD spectroscopy indicated a variable conformation for the N- and C-terminal regions. NDRG1 binds to various types of lipid vesicles, and the conformation of the C-terminal region is modulated upon lipid interaction. Intriguingly, NDRG1 interacts with metal ions, such as nickel, but is prone to aggregation in their presence. Our results uncover the structural and dynamic features of NDRG1, as well as elucidate its interactions with metals and lipids, and encourage studies to identify a putative hydrolase activity of NDRG1.
Crystal and solution structure of NDRG1, a membrane-binding protein linked to myelination and tumour suppression.,Mustonen V, Muruganandam G, Loris R, Kursula P, Ruskamo S FEBS J. 2020 Dec 10. doi: 10.1111/febs.15660. PMID:33305529[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kim KT, Ongusaha PP, Hong YK, Kurdistani SK, Nakamura M, Lu KP, Lee SW. Function of Drg1/Rit42 in p53-dependent mitotic spindle checkpoint. J Biol Chem. 2004 Sep 10;279(37):38597-602. doi: 10.1074/jbc.M400781200. Epub, 2004 Jul 9. PMID:15247272 doi:http://dx.doi.org/10.1074/jbc.M400781200
- ↑ Stein S, Thomas EK, Herzog B, Westfall MD, Rocheleau JV, Jackson RS 2nd, Wang M, Liang P. NDRG1 is necessary for p53-dependent apoptosis. J Biol Chem. 2004 Nov 19;279(47):48930-40. doi: 10.1074/jbc.M400386200. Epub 2004, Sep 17. PMID:15377670 doi:http://dx.doi.org/10.1074/jbc.M400386200
- ↑ Kachhap SK, Faith D, Qian DZ, Shabbeer S, Galloway NL, Pili R, Denmeade SR, DeMarzo AM, Carducci MA. The N-Myc down regulated Gene1 (NDRG1) Is a Rab4a effector involved in vesicular recycling of E-cadherin. PLoS One. 2007 Sep 5;2(9):e844. doi: 10.1371/journal.pone.0000844. PMID:17786215 doi:http://dx.doi.org/10.1371/journal.pone.0000844
- ↑ Kurdistani SK, Arizti P, Reimer CL, Sugrue MM, Aaronson SA, Lee SW. Inhibition of tumor cell growth by RTP/rit42 and its responsiveness to p53 and DNA damage. Cancer Res. 1998 Oct 1;58(19):4439-44. PMID:9766676
- ↑ Mustonen V, Muruganandam G, Loris R, Kursula P, Ruskamo S. Crystal and solution structure of NDRG1, a membrane-binding protein linked to myelination and tumour suppression. FEBS J. 2020 Dec 10. doi: 10.1111/febs.15660. PMID:33305529 doi:http://dx.doi.org/10.1111/febs.15660
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