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| | ==Molecular structure of FUS low sequence complexity domain protein fibrils== | | ==Molecular structure of FUS low sequence complexity domain protein fibrils== |
| - | <StructureSection load='5w3n' size='340' side='right'caption='[[5w3n]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='5w3n' size='340' side='right'caption='[[5w3n]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5w3n]] is a 9 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W3N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W3N FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5w3n]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W3N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5W3N FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FUS, TLS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </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=5w3n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w3n OCA], [https://pdbe.org/5w3n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5w3n RCSB], [https://www.ebi.ac.uk/pdbsum/5w3n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5w3n ProSAT]</span></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=5w3n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w3n OCA], [http://pdbe.org/5w3n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w3n RCSB], [http://www.ebi.ac.uk/pdbsum/5w3n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w3n ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/FUS_HUMAN FUS_HUMAN]] Frontotemporal dementia with motor neuron disease;Hereditary essential tremor;Amyotrophic lateral sclerosis;Juvenile amyotrophic lateral sclerosis;Myxofibrosarcoma;Myxoid/round cell liposarcoma. A chromosomal aberration involving FUS is found in a patient with malignant myxoid liposarcoma. Translocation t(12;16)(q13;p11) with DDIT3. A chromosomal aberration involving FUS is a cause of acute myeloid leukemia (AML). Translocation t(16;21)(p11;q22) with ERG. The disease may be caused by mutations affecting the gene represented in this entry. A chromosomal aberration involving FUS is found in a patient with angiomatoid fibrous histiocytoma. Translocation t(12;16)(q13;p11.2) with ATF1 generates a chimeric FUS/ATF1 protein. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/FUS_HUMAN FUS_HUMAN] Frontotemporal dementia with motor neuron disease;Hereditary essential tremor;Amyotrophic lateral sclerosis;Juvenile amyotrophic lateral sclerosis;Myxofibrosarcoma;Myxoid/round cell liposarcoma. A chromosomal aberration involving FUS is found in a patient with malignant myxoid liposarcoma. Translocation t(12;16)(q13;p11) with DDIT3. A chromosomal aberration involving FUS is a cause of acute myeloid leukemia (AML). Translocation t(16;21)(p11;q22) with ERG. The disease may be caused by mutations affecting the gene represented in this entry. A chromosomal aberration involving FUS is found in a patient with angiomatoid fibrous histiocytoma. Translocation t(12;16)(q13;p11.2) with ATF1 generates a chimeric FUS/ATF1 protein. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FUS_HUMAN FUS_HUMAN]] Binds both single-stranded and double-stranded DNA and promotes ATP-independent annealing of complementary single-stranded DNAs and D-loop formation in superhelical double-stranded DNA. May play a role in maintenance of genomic integrity. | + | [https://www.uniprot.org/uniprot/FUS_HUMAN FUS_HUMAN] Binds both single-stranded and double-stranded DNA and promotes ATP-independent annealing of complementary single-stranded DNAs and D-loop formation in superhelical double-stranded DNA. May play a role in maintenance of genomic integrity. |
| | <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: Hung, I]] | + | [[Category: Hung I]] |
| - | [[Category: Kato, M]] | + | [[Category: Kato M]] |
| - | [[Category: Lin, Y]] | + | [[Category: Lin Y]] |
| - | [[Category: McKnight, S]] | + | [[Category: McKnight S]] |
| - | [[Category: Murray, D T]] | + | [[Category: Murray DT]] |
| - | [[Category: Thurber, K]] | + | [[Category: Thurber K]] |
| - | [[Category: Tycko, R]] | + | [[Category: Tycko R]] |
| - | [[Category: Intrinsically disordered protein]]
| + | |
| - | [[Category: Low complexity sequence domain]]
| + | |
| - | [[Category: Protein fibril]]
| + | |
| - | [[Category: Rna granule]]
| + | |
| - | [[Category: Rna transport]]
| + | |
| Structural highlights
Disease
FUS_HUMAN Frontotemporal dementia with motor neuron disease;Hereditary essential tremor;Amyotrophic lateral sclerosis;Juvenile amyotrophic lateral sclerosis;Myxofibrosarcoma;Myxoid/round cell liposarcoma. A chromosomal aberration involving FUS is found in a patient with malignant myxoid liposarcoma. Translocation t(12;16)(q13;p11) with DDIT3. A chromosomal aberration involving FUS is a cause of acute myeloid leukemia (AML). Translocation t(16;21)(p11;q22) with ERG. The disease may be caused by mutations affecting the gene represented in this entry. A chromosomal aberration involving FUS is found in a patient with angiomatoid fibrous histiocytoma. Translocation t(12;16)(q13;p11.2) with ATF1 generates a chimeric FUS/ATF1 protein. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
Function
FUS_HUMAN Binds both single-stranded and double-stranded DNA and promotes ATP-independent annealing of complementary single-stranded DNAs and D-loop formation in superhelical double-stranded DNA. May play a role in maintenance of genomic integrity.
Publication Abstract from PubMed
Polymerization and phase separation of proteins containing low-complexity (LC) domains are important factors in gene expression, mRNA processing and trafficking, and localization of translation. We have used solid-state nuclear magnetic resonance methods to characterize the molecular structure of self-assembling fibrils formed by the LC domain of the fused in sarcoma (FUS) RNA-binding protein. From the 214-residue LC domain of FUS (FUS-LC), a segment of only 57 residues forms the fibril core, while other segments remain dynamically disordered. Unlike pathogenic amyloid fibrils, FUS-LC fibrils lack hydrophobic interactions within the core and are not polymorphic at the molecular structural level. Phosphorylation of core-forming residues by DNA-dependent protein kinase blocks binding of soluble FUS-LC to FUS-LC hydrogels and dissolves phase-separated, liquid-like FUS-LC droplets. These studies offer a structural basis for understanding LC domain self-assembly, phase separation, and regulation by post-translational modification.
Structure of FUS Protein Fibrils and Its Relevance to Self-Assembly and Phase Separation of Low-Complexity Domains.,Murray DT, Kato M, Lin Y, Thurber KR, Hung I, McKnight SL, Tycko R Cell. 2017 Oct 19;171(3):615-627.e16. doi: 10.1016/j.cell.2017.08.048. Epub 2017 , Sep 21. PMID:28942918[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Murray DT, Kato M, Lin Y, Thurber KR, Hung I, McKnight SL, Tycko R. Structure of FUS Protein Fibrils and Its Relevance to Self-Assembly and Phase Separation of Low-Complexity Domains. Cell. 2017 Oct 19;171(3):615-627.e16. doi: 10.1016/j.cell.2017.08.048. Epub 2017 , Sep 21. PMID:28942918 doi:http://dx.doi.org/10.1016/j.cell.2017.08.048
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