|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal structure of TRF1 and TERB1== | | ==Crystal structure of TRF1 and TERB1== |
| - | <StructureSection load='5xup' size='340' side='right' caption='[[5xup]], [[Resolution|resolution]] 2.10Å' scene=''> | + | <StructureSection load='5xup' size='340' side='right'caption='[[5xup]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5xup]] 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=5XUP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XUP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5xup]] is a 4 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=5XUP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XUP FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TERF1, PIN2, TRBF1, TRF, TRF1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TERB1, CCDC79 ([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]] 2.1Å</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=5xup FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xup OCA], [http://pdbe.org/5xup PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xup RCSB], [http://www.ebi.ac.uk/pdbsum/5xup PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xup 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=5xup FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xup OCA], [https://pdbe.org/5xup PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xup RCSB], [https://www.ebi.ac.uk/pdbsum/5xup PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xup ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TERF1_HUMAN TERF1_HUMAN]] Binds the telomeric double-stranded TTAGGG repeat and negatively regulates telomere length. Involved in the regulation of the mitotic spindle. Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded TTAGGG repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways.<ref>PMID:16166375</ref> [[http://www.uniprot.org/uniprot/TERB1_HUMAN TERB1_HUMAN]] Meiosis-specific telomere-associated protein involved in meiotic telomere attachment to the nucleus inner membrane, a crucial step for homologous pairing and synapsis. Component of the MAJIN-TERB1-TERB2 complex, which promotes telomere cap exchange by mediating attachment of telomeric DNA to the inner nuclear membrane and replacement of the protective cap of telomeric chromosomes: in early meiosis, the MAJIN-TERB1-TERB2 complex associates with telomeric DNA and the shelterin/telosome complex. During prophase, the complex matures and promotes release of the shelterin/telosome complex from telomeric DNA. In the MAJIN-TERB1-TERB2 complex, TERB1 probably mediates association with the shelterin/telosome complex via interaction with TERF1, promoting priming telomeric DNA attachment'. Promotes telomere association with the nuclear envelope and deposition of the SUN-KASH/LINC complex. Also recruits cohesin to telomeres to develop structural rigidity.[UniProtKB:Q8C0V1] | + | [https://www.uniprot.org/uniprot/TERF1_HUMAN TERF1_HUMAN] Binds the telomeric double-stranded TTAGGG repeat and negatively regulates telomere length. Involved in the regulation of the mitotic spindle. Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded TTAGGG repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways.<ref>PMID:16166375</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 22: |
Line 22: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Huang, C]] | + | [[Category: Large Structures]] |
| - | [[Category: Lei, M]] | + | [[Category: Huang C]] |
| - | [[Category: Long, J]] | + | [[Category: Lei M]] |
| - | [[Category: Wu, J]] | + | [[Category: Long J]] |
| - | [[Category: Dna binding protein]]
| + | [[Category: Wu J]] |
| - | [[Category: Meiosis]]
| + | |
| - | [[Category: Telomere]]
| + | |
| Structural highlights
Function
TERF1_HUMAN Binds the telomeric double-stranded TTAGGG repeat and negatively regulates telomere length. Involved in the regulation of the mitotic spindle. Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded TTAGGG repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways.[1]
Publication Abstract from PubMed
During meiotic prophase, the meiosis-specific telomere-binding protein TERB1 regulates chromosome movement required for homologous pairing and recombination by interacting with the telomeric shelterin subunit TRF1. Here, we report the crystal structure of the TRF1-binding motif of human TERB1 in complex with the TRFH domain of TRF1. Notably, specific disruption of the TERB1-TRF1 interaction by a point mutation in the mouse Terb1 gene results in infertility only in males. We find that this mutation causes an arrest in the zygotene-early pachytene stage and mild telomere abnormalities of autosomes but unpaired X and Y chromosomes in pachytene, leading to massive spermatocyte apoptosis. We propose that the loss of telomere structure mediated by the TERB1-TRF1 interaction significantly affects homologous pairing of the telomere-adjacent pseudoautosomal region (PAR) of the X and Y chromosomes in mouse spermatocytes. Our findings uncover a specific mechanism of telomeres that surmounts the unique challenges of mammalian X-Y pairing in meiosis.
Telomeric TERB1-TRF1 interaction is crucial for male meiosis.,Long J, Huang C, Chen Y, Zhang Y, Shi S, Wu L, Liu Y, Liu C, Wu J, Lei M Nat Struct Mol Biol. 2017 Dec;24(12):1073-1080. doi: 10.1038/nsmb.3496. Epub 2017, Oct 30. PMID:29083416[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ de Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev. 2005 Sep 15;19(18):2100-10. PMID:16166375 doi:10.1101/gad.1346005
- ↑ Long J, Huang C, Chen Y, Zhang Y, Shi S, Wu L, Liu Y, Liu C, Wu J, Lei M. Telomeric TERB1-TRF1 interaction is crucial for male meiosis. Nat Struct Mol Biol. 2017 Dec;24(12):1073-1080. doi: 10.1038/nsmb.3496. Epub 2017, Oct 30. PMID:29083416 doi:http://dx.doi.org/10.1038/nsmb.3496
|
