7P05

Cryo-EM structure of Pdr5 from Saccharomyces cerevisiae in inward-facing conformation with ADP/ATP and rhodamine 6G


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.13 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


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Literature

Structure and efflux mechanism of the yeast pleiotropic drug resistance transporter Pdr5.

Harris, A.Wagner, M.Du, D.Raschka, S.Nentwig, L.M.Gohlke, H.Smits, S.H.J.Luisi, B.F.Schmitt, L.

(2021) Nat Commun 12: 5254-5254

  • DOI: https://doi.org/10.1038/s41467-021-25574-8
  • Primary Citation of Related Structures:  
    7P03, 7P04, 7P05, 7P06

  • PubMed Abstract: 

    Pdr5, a member of the extensive ABC transporter superfamily, is representative of a clinically relevant subgroup involved in pleiotropic drug resistance. Pdr5 and its homologues drive drug efflux through uncoupled hydrolysis of nucleotides, enabling organisms such as baker's yeast and pathogenic fungi to survive in the presence of chemically diverse antifungal agents. Here, we present the molecular structure of Pdr5 solved with single particle cryo-EM, revealing details of an ATP-driven conformational cycle, which mechanically drives drug translocation through an amphipathic channel, and a clamping switch within a conserved linker loop that acts as a nucleotide sensor. One half of the transporter remains nearly invariant throughout the cycle, while its partner undergoes changes that are transmitted across inter-domain interfaces to support a peristaltic motion of the pumped molecule. The efflux model proposed here rationalises the pleiotropic impact of Pdr5 and opens new avenues for the development of effective antifungal compounds.


  • Organizational Affiliation

    Department of Biochemistry, University of Cambridge, Cambridge, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Pleiotropic ABC efflux transporter of multiple drugs1,511Saccharomyces cerevisiae S288CMutation(s): 0 
Membrane Entity: Yes 
UniProt
Find proteins for P33302 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c))
Explore P33302 
Go to UniProtKB:  P33302
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP33302
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.13 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 
EM Software:
TaskSoftware PackageVersion
MODEL REFINEMENTPHENIX1.18.2
RECONSTRUCTIONRELION3.1

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
European Research Council (ERC)United Kingdom742210

Revision History  (Full details and data files)

  • Version 1.0: 2021-11-10
    Type: Initial release