7N73

Cryo-EM structure of ATP13A2 in the ADP-AlF-bound E1P-ADP-like state


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 2.90 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structural basis of polyamine transport by human ATP13A2 (PARK9).

Sim, S.I.von Bulow, S.Hummer, G.Park, E.

(2021) Mol Cell 81: 4635-4649.e8

  • DOI: https://doi.org/10.1016/j.molcel.2021.08.017
  • Primary Citation of Related Structures:  
    7N70, 7N72, 7N73, 7N74, 7N75, 7N76, 7N77, 7N78

  • PubMed Abstract: 

    Polyamines are small, organic polycations that are ubiquitous and essential to all forms of life. Currently, how polyamines are transported across membranes is not understood. Recent studies have suggested that ATP13A2 and its close homologs, collectively known as P5B-ATPases, are polyamine transporters at endo-/lysosomes. Loss-of-function mutations of ATP13A2 in humans cause hereditary early-onset Parkinson's disease. To understand the polyamine transport mechanism of ATP13A2, we determined high-resolution cryoelectron microscopy (cryo-EM) structures of human ATP13A2 in five distinct conformational intermediates, which together, represent a near-complete transport cycle of ATP13A2. The structural basis of the polyamine specificity was revealed by an endogenous polyamine molecule bound to a narrow, elongated cavity within the transmembrane domain. The structures show an atypical transport path for a water-soluble substrate, in which polyamines may exit within the cytosolic leaflet of the membrane. Our study provides important mechanistic insights into polyamine transport and a framework to understand the functions and mechanisms of P5B-ATPases.


  • Organizational Affiliation

    Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Isoform 3 of Polyamine-transporting ATPase 13A21,175Homo sapiensMutation(s): 0 
Gene Names: ATP13A2PARK9
EC: 7.6.2
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for Q9NQ11 (Homo sapiens)
Explore Q9NQ11 
Go to UniProtKB:  Q9NQ11
PHAROS:  Q9NQ11
GTEx:  ENSG00000159363 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9NQ11
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
Y01
Query on Y01

Download Ideal Coordinates CCD File 
F [auth A],
G [auth A]
CHOLESTEROL HEMISUCCINATE
C31 H50 O4
WLNARFZDISHUGS-MIXBDBMTSA-N
ADP (Subject of Investigation/LOI)
Query on ADP

Download Ideal Coordinates CCD File 
B [auth A]ADENOSINE-5'-DIPHOSPHATE
C10 H15 N5 O10 P2
XTWYTFMLZFPYCI-KQYNXXCUSA-N
ALF (Subject of Investigation/LOI)
Query on ALF

Download Ideal Coordinates CCD File 
C [auth A]TETRAFLUOROALUMINATE ION
Al F4
UYOMQIYKOOHAMK-UHFFFAOYSA-J
MG (Subject of Investigation/LOI)
Query on MG

Download Ideal Coordinates CCD File 
D [auth A],
E [auth A]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 2.90 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 
EM Software:
TaskSoftware PackageVersion
RECONSTRUCTIONcryoSPARC2.15

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Other privateUnited States--

Revision History  (Full details and data files)

  • Version 1.0: 2021-11-10
    Type: Initial release
  • Version 1.1: 2021-12-01
    Changes: Database references
  • Version 1.2: 2024-05-29
    Changes: Data collection