5J1S

TorsinA-LULL1 complex, H. sapiens, bound to VHH-BS2


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.188 
  • R-Value Work: 0.143 
  • R-Value Observed: 0.144 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Structures of TorsinA and its disease-mutant complexed with an activator reveal the molecular basis for primary dystonia.

Demircioglu, F.E.Sosa, B.A.Ingram, J.Ploegh, H.L.Schwartz, T.U.

(2016) Elife 5

  • DOI: https://doi.org/10.7554/eLife.17983
  • Primary Citation of Related Structures:  
    5J1S, 5J1T

  • PubMed Abstract: 

    The most common cause of early onset primary dystonia, a neuromuscular disease, is a glutamate deletion (ΔE) at position 302/303 of TorsinA, a AAA+ ATPase that resides in the endoplasmic reticulum. While the function of TorsinA remains elusive, the ΔE mutation is known to diminish binding of two TorsinA ATPase activators: lamina-associated protein 1 (LAP1) and its paralog, luminal domain like LAP1 (LULL1). Using a nanobody as a crystallization chaperone, we obtained a 1.4 Å crystal structure of human TorsinA in complex with LULL1. This nanobody likewise stabilized the weakened TorsinAΔE-LULL1 interaction, which enabled us to solve its structure at 1.4 Å also. A comparison of these structures shows, in atomic detail, the subtle differences in activator interactions that separate the healthy from the diseased state. This information may provide a structural platform for drug development, as a small molecule that rescues TorsinAΔE could serve as a cure for primary dystonia.


  • Organizational Affiliation

    Department of Biology, Massachusetts Institute of Technology, Cambridge, United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Torsin-1A284Homo sapiensMutation(s): 1 
Gene Names: TOR1ADQ2DYT1TATORA
EC: 3.6.4
UniProt & NIH Common Fund Data Resources
Find proteins for O14656 (Homo sapiens)
Explore O14656 
Go to UniProtKB:  O14656
PHAROS:  O14656
GTEx:  ENSG00000136827 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO14656
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Torsin-1A-interacting protein 2239Homo sapiensMutation(s): 0 
Gene Names: TOR1AIP2IFRG15LULL1
UniProt & NIH Common Fund Data Resources
Find proteins for Q8NFQ8 (Homo sapiens)
Explore Q8NFQ8 
Go to UniProtKB:  Q8NFQ8
PHAROS:  Q8NFQ8
GTEx:  ENSG00000169905 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8NFQ8
Sequence Annotations
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
VHH domain BS-2123Vicugna pacosMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

Unit Cell:
Length ( Å )Angle ( ˚ )
a = 75.739α = 90
b = 90.659β = 90
c = 105.092γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
PDB_EXTRACTdata extraction
HKL-2000data reduction
SCALEPACKdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH/NIAMS)United StatesAR065484

Revision History  (Full details and data files)

  • Version 1.0: 2016-08-17
    Type: Initial release
  • Version 1.1: 2017-09-20
    Changes: Author supporting evidence, Derived calculations
  • Version 1.2: 2019-12-11
    Changes: Author supporting evidence