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6gbm

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Solution structure of FUS-RRM bound to stem-loop RNA

Structural highlights

6gbm is a 2 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	FUS, TLS (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

Fused in sarcoma (FUS) is an RNA binding protein involved in regulating many aspects of RNA processing and linked to several neurodegenerative diseases. Transcriptomics studies indicate that FUS binds a large variety of RNA motifs, suggesting that FUS RNA binding might be quite complex. Here, we present solution structures of FUS zinc finger (ZnF) and RNA recognition motif (RRM) domains bound to RNA. These structures show a bipartite binding mode of FUS comprising of sequence-specific recognition of a NGGU motif via the ZnF and an unusual shape recognition of a stem-loop RNA via the RRM. In addition, sequence-independent interactions via the RGG repeats significantly increase binding affinity and promote destabilization of structured RNA conformation, enabling additional binding. We further show that disruption of the RRM and ZnF domains abolishes FUS function in splicing. Altogether, our results rationalize why deciphering the RNA binding mode of FUS has been so challenging.

The Solution Structure of FUS Bound to RNA Reveals a Bipartite Mode of RNA Recognition with Both Sequence and Shape Specificity.,Loughlin FE, Lukavsky PJ, Kazeeva T, Reber S, Hock EM, Colombo M, Von Schroetter C, Pauli P, Clery A, Muhlemann O, Polymenidou M, Ruepp MD, Allain FH Mol Cell. 2019 Feb 7;73(3):490-504.e6. doi: 10.1016/j.molcel.2018.11.012. Epub, 2018 Dec 20. PMID:30581145^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Loughlin FE, Lukavsky PJ, Kazeeva T, Reber S, Hock EM, Colombo M, Von Schroetter C, Pauli P, Clery A, Muhlemann O, Polymenidou M, Ruepp MD, Allain FH. The Solution Structure of FUS Bound to RNA Reveals a Bipartite Mode of RNA Recognition with Both Sequence and Shape Specificity. Mol Cell. 2019 Feb 7;73(3):490-504.e6. doi: 10.1016/j.molcel.2018.11.012. Epub, 2018 Dec 20. PMID:30581145 doi:http://dx.doi.org/10.1016/j.molcel.2018.11.012

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6gbm"

@@ Line 1: / Line 1: @@
 ==Solution structure of FUS-RRM bound to stem-loop RNA==
-<StructureSection load='6gbm' size='340' side='right' caption='[[6gbm]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='6gbm' size='340' side='right'caption='[[6gbm]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6gbm]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GBM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GBM FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6gbm]] is a 2 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=6GBM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GBM FirstGlance]. <br>
-</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=6gbm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gbm OCA], [http://pdbe.org/6gbm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gbm RCSB], [http://www.ebi.ac.uk/pdbsum/6gbm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gbm ProSAT]</span></td></tr>
+</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>
+<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=6gbm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gbm OCA], [http://pdbe.org/6gbm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gbm RCSB], [http://www.ebi.ac.uk/pdbsum/6gbm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gbm ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Allain, F H.T]]
 [[Category: Loughlin, F E]]

6gbm

From Proteopedia

Current revision

Solution structure of FUS-RRM bound to stem-loop RNA

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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