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| | ==Crystal structure of the DNA-binding domain of human myelin-gene regulatory factor== | | ==Crystal structure of the DNA-binding domain of human myelin-gene regulatory factor== |
| - | <StructureSection load='5zhu' size='340' side='right' caption='[[5zhu]], [[Resolution|resolution]] 2.20Å' scene=''> | + | <StructureSection load='5zhu' size='340' side='right'caption='[[5zhu]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5zhu]] is a 3 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=5ZHU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZHU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5zhu]] is a 3 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=5ZHU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZHU FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MYRF, C11orf9, KIAA0954, MRF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 2.202Å</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=5zhu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zhu OCA], [http://pdbe.org/5zhu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zhu RCSB], [http://www.ebi.ac.uk/pdbsum/5zhu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zhu 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=5zhu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zhu OCA], [https://pdbe.org/5zhu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zhu RCSB], [https://www.ebi.ac.uk/pdbsum/5zhu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zhu ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MYRF_HUMAN MYRF_HUMAN]] Myelin regulatory factor: Constitutes a precursor of the transcription factor. Mediates the autocatalytic cleavage that releases the Myelin regulatory factor, N-terminal component that specifically activates transcription of central nervous system (CNS) myelin genes (PubMed:23966832).<ref>PMID:23966832</ref> Myelin regulatory factor, C-terminal: Membrane-bound part that has no transcription factor activity and remains attached to the endoplasmic reticulum membrane following cleavage.<ref>PMID:23966832</ref> Myelin regulatory factor, N-terminal: Transcription factor that specifically activates expression of myelin genes such as MBP, MOG, MAG, DUSP15 and PLP1 during oligodendrocyte (OL) maturation, thereby playing a central role in oligodendrocyte maturation and CNS myelination. Specifically recognizes and binds DNA sequence 5'-CTGGYAC-3' in the regulatory regions of myelin-specific genes and directly activates their expression. Not only required during oligodendrocyte differentiation but is also required on an ongoing basis for the maintenance of expression of myelin genes and for the maintenance of a mature, viable oligodendrocyte phenotype (PubMed:23966832).<ref>PMID:23966832</ref> | + | [https://www.uniprot.org/uniprot/MYRF_HUMAN MYRF_HUMAN] Myelin regulatory factor: Constitutes a precursor of the transcription factor. Mediates the autocatalytic cleavage that releases the Myelin regulatory factor, N-terminal component that specifically activates transcription of central nervous system (CNS) myelin genes (PubMed:23966832).<ref>PMID:23966832</ref> Myelin regulatory factor, C-terminal: Membrane-bound part that has no transcription factor activity and remains attached to the endoplasmic reticulum membrane following cleavage.<ref>PMID:23966832</ref> Myelin regulatory factor, N-terminal: Transcription factor that specifically activates expression of myelin genes such as MBP, MOG, MAG, DUSP15 and PLP1 during oligodendrocyte (OL) maturation, thereby playing a central role in oligodendrocyte maturation and CNS myelination. Specifically recognizes and binds DNA sequence 5'-CTGGYAC-3' in the regulatory regions of myelin-specific genes and directly activates their expression. Not only required during oligodendrocyte differentiation but is also required on an ongoing basis for the maintenance of expression of myelin genes and for the maintenance of a mature, viable oligodendrocyte phenotype (PubMed:23966832).<ref>PMID:23966832</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: Chen, B]] | + | [[Category: Large Structures]] |
| - | [[Category: Ye, S]] | + | [[Category: Chen B]] |
| - | [[Category: Zhang, R]] | + | [[Category: Ye S]] |
| - | [[Category: Zhu, Y]] | + | [[Category: Zhang R]] |
| - | [[Category: Dna-binding domain]]
| + | [[Category: Zhu Y]] |
| - | [[Category: Myelingene regulatory factor]]
| + | |
| - | [[Category: Transcription]]
| + | |
| Structural highlights
Function
MYRF_HUMAN Myelin regulatory factor: Constitutes a precursor of the transcription factor. Mediates the autocatalytic cleavage that releases the Myelin regulatory factor, N-terminal component that specifically activates transcription of central nervous system (CNS) myelin genes (PubMed:23966832).[1] Myelin regulatory factor, C-terminal: Membrane-bound part that has no transcription factor activity and remains attached to the endoplasmic reticulum membrane following cleavage.[2] Myelin regulatory factor, N-terminal: Transcription factor that specifically activates expression of myelin genes such as MBP, MOG, MAG, DUSP15 and PLP1 during oligodendrocyte (OL) maturation, thereby playing a central role in oligodendrocyte maturation and CNS myelination. Specifically recognizes and binds DNA sequence 5'-CTGGYAC-3' in the regulatory regions of myelin-specific genes and directly activates their expression. Not only required during oligodendrocyte differentiation but is also required on an ongoing basis for the maintenance of expression of myelin genes and for the maintenance of a mature, viable oligodendrocyte phenotype (PubMed:23966832).[3]
Publication Abstract from PubMed
Myelin-gene regulatory factor (MYRF) is a membrane-bound transcription factors, which is responsible for the differentiation of oligodendrocytes and myelination of central nervous system. Followed by a self-cleavage by the intramolecular chaperone auto-processing (ICA) domain, DNA-binding domain (DBD) of MYRF is released from the endoplasmic reticulum (ER) and was then translocated to the nucleus to regulate gene expression. In present work, we have solved the crystal structure of the human MYRF-DBD to 1.85-A resolution. It exhibits a typical s-type Ig-fold and packs as symmetric trimeric form in the crystal via hydrogen-bond networks in three regions. Accordingly, we identified a couple of key residues on MYRF-DBD, which might play important roles in DNA-binding, in particular Arg521 on its C-terminal tail. The R521A mutant of DBD showed only 17% affinity to dsDNA targets compared to wild-type DBD. Then we built a plausible protein-DNA binding model of MYRF-DBD, which will help to elucidate its mechanism in DNA-binding and transcriptional regulation.
Structure of the DNA-binding domain of human myelin-gene regulatory factor reveals its potential protein-DNA recognition mode.,Chen B, Zhu Y, Ye S, Zhang R J Struct Biol. 2018 May 2. pii: S1047-8477(18)30115-1. doi:, 10.1016/j.jsb.2018.04.007. PMID:29729323[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Li Z, Park Y, Marcotte EM. A Bacteriophage tailspike domain promotes self-cleavage of a human membrane-bound transcription factor, the myelin regulatory factor MYRF. PLoS Biol. 2013;11(8):e1001624. doi: 10.1371/journal.pbio.1001624. Epub 2013 Aug , 13. PMID:23966832 doi:http://dx.doi.org/10.1371/journal.pbio.1001624
- ↑ Li Z, Park Y, Marcotte EM. A Bacteriophage tailspike domain promotes self-cleavage of a human membrane-bound transcription factor, the myelin regulatory factor MYRF. PLoS Biol. 2013;11(8):e1001624. doi: 10.1371/journal.pbio.1001624. Epub 2013 Aug , 13. PMID:23966832 doi:http://dx.doi.org/10.1371/journal.pbio.1001624
- ↑ Li Z, Park Y, Marcotte EM. A Bacteriophage tailspike domain promotes self-cleavage of a human membrane-bound transcription factor, the myelin regulatory factor MYRF. PLoS Biol. 2013;11(8):e1001624. doi: 10.1371/journal.pbio.1001624. Epub 2013 Aug , 13. PMID:23966832 doi:http://dx.doi.org/10.1371/journal.pbio.1001624
- ↑ Chen B, Zhu Y, Ye S, Zhang R. Structure of the DNA-binding domain of human myelin-gene regulatory factor reveals its potential protein-DNA recognition mode. J Struct Biol. 2018 May 2. pii: S1047-8477(18)30115-1. doi:, 10.1016/j.jsb.2018.04.007. PMID:29729323 doi:http://dx.doi.org/10.1016/j.jsb.2018.04.007
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