6G99

Solution structure of FUS-ZnF bound to UGGUG


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 500 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

The Solution Structure of FUS Bound to RNA Reveals a Bipartite Mode of RNA Recognition with Both Sequence and Shape Specificity.

Loughlin, F.E.Lukavsky, P.J.Kazeeva, T.Reber, S.Hock, E.M.Colombo, M.Von Schroetter, C.Pauli, P.Clery, A.Muhlemann, O.Polymenidou, M.Ruepp, M.D.Allain, F.H.

(2019) Mol Cell 73: 490-504.e6

  • DOI: https://doi.org/10.1016/j.molcel.2018.11.012
  • Primary Citation of Related Structures:  
    6G99, 6GBM

  • PubMed Abstract: 

    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.


  • Organizational Affiliation

    Department of Biology, Institute of Molecular Biology and Biophysics, ETH Zürich, 8093 Zürich, Switzerland; Monash Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Clayton, 3800 VIC, Australia. Electronic address: fionna.loughlin@monash.edu.


Macromolecules

Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
RNA-binding protein FUSA [auth B]41Homo sapiensMutation(s): 0 
Gene Names: FUSTLS
UniProt & NIH Common Fund Data Resources
Find proteins for P35637 (Homo sapiens)
Explore P35637 
Go to UniProtKB:  P35637
PHAROS:  P35637
GTEx:  ENSG00000089280 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP35637
Sequence Annotations
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  • Reference Sequence

Find similar nucleic acids by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains LengthOrganismImage
RNA (5'-R(*UP*GP*GP*UP*G)-3')B [auth A]5Homo sapiens
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ZN
Query on ZN

Download Ideal Coordinates CCD File 
C [auth B]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 500 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2019-02-20
    Type: Initial release
  • Version 1.1: 2019-05-08
    Changes: Data collection
  • Version 1.2: 2024-05-15
    Changes: Data collection, Database references