6B9E

Human ATL1 mutant - R77A / F151S bound to GDP


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.99 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.203 
  • R-Value Observed: 0.204 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

A hereditary spastic paraplegia-associated atlastin variant exhibits defective allosteric coupling in the catalytic core.

O'Donnell, J.P.Byrnes, L.J.Cooley, R.B.Sondermann, H.

(2018) J Biol Chem 293: 687-700

  • DOI: https://doi.org/10.1074/jbc.RA117.000380
  • Primary Citation of Related Structures:  
    6B9D, 6B9E, 6B9F, 6B9G

  • PubMed Abstract: 

    The dynamin-related GTPase atlastin (ATL) catalyzes membrane fusion of the endoplasmic reticulum and thus establishes a network of branched membrane tubules. When ATL function is compromised, the morphology of the endoplasmic reticulum deteriorates, and these defects can result in neurological disorders such as hereditary spastic paraplegia and hereditary sensory neuropathy. ATLs harness the energy of GTP hydrolysis to initiate a series of conformational changes that enable homodimerization and subsequent membrane fusion. Disease-associated amino acid substitutions cluster in regions adjacent to ATL's catalytic site, but the consequences for the GTPase's molecular mechanism are often poorly understood. Here, we elucidate structural and functional defects of an atypical hereditary spastic paraplegia mutant, ATL1-F151S, that is impaired in its nucleotide-hydrolysis cycle but can still adopt a high-affinity homodimer when bound to a transition-state analog. Crystal structures of mutant proteins yielded models of the monomeric pre- and post-hydrolysis states of ATL. Together, these findings define a mechanism for allosteric coupling in which Phe 151 is the central residue in a hydrophobic interaction network connecting the active site to an interdomain interface responsible for nucleotide loading.


  • Organizational Affiliation

    From the Department of Molecular Medicine, Cornell University, Ithaca, New York 14853.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Atlastin-1
A, B
458Homo sapiensMutation(s): 2 
Gene Names: ATL1GBP3SPG3A
EC: 3.6.5
UniProt & NIH Common Fund Data Resources
Find proteins for Q8WXF7 (Homo sapiens)
Explore Q8WXF7 
Go to UniProtKB:  Q8WXF7
PHAROS:  Q8WXF7
GTEx:  ENSG00000198513 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8WXF7
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.99 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.203 
  • R-Value Observed: 0.204 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 52.062α = 116.85
b = 68.107β = 90.77
c = 76.016γ = 98.5
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
SCALAdata scaling
PHENIXphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Spastic Paraplegia FoundationUnited States--

Revision History  (Full details and data files)

  • Version 1.0: 2017-12-06
    Type: Initial release
  • Version 1.1: 2018-01-31
    Changes: Database references
  • Version 1.2: 2023-10-04
    Changes: Data collection, Database references, Derived calculations, Refinement description