4U8V

Coupling of remote alternating-access transport mechanisms for protons and substrates in the multidrug efflux pump AcrB


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.191 
  • R-Value Observed: 0.193 

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Ligand Structure Quality Assessment 


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Literature

Coupling of remote alternating-access transport mechanisms for protons and substrates in the multidrug efflux pump AcrB.

Eicher, T.Seeger, M.A.Anselmi, C.Zhou, W.Brandstatter, L.Verrey, F.Diederichs, K.Faraldo-Gomez, J.D.Pos, K.M.

(2014) Elife 3

  • DOI: https://doi.org/10.7554/eLife.03145
  • Primary Citation of Related Structures:  
    4U8V, 4U8Y, 4U95, 4U96

  • PubMed Abstract: 

    Membrane transporters of the RND superfamily confer multidrug resistance to pathogenic bacteria, and are essential for cholesterol metabolism and embryonic development in humans. We use high-resolution X-ray crystallography and computational methods to delineate the mechanism of the homotrimeric RND-type proton/drug antiporter AcrB, the active component of the major efflux system AcrAB-TolC in Escherichia coli, and one most complex and intriguing membrane transporters known to date. Analysis of wildtype AcrB and four functionally-inactive variants reveals an unprecedented mechanism that involves two remote alternating-access conformational cycles within each protomer, namely one for protons in the transmembrane region and another for drugs in the periplasmic domain, 50 Å apart. Each of these cycles entails two distinct types of collective motions of two structural repeats, coupled by flanking α-helices that project from the membrane. Moreover, we rationalize how the cross-talk among protomers across the trimerization interface might lead to a more kinetically efficient efflux system.


  • Organizational Affiliation

    Institute of Biochemistry, Goethe University, Frankfurt am Main, Germany.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Multidrug efflux pump subunit AcrB
A, B, C
1,057Escherichia coliMutation(s): 1 
Gene Names: acrBacrEb0462JW0451
Membrane Entity: Yes 
UniProt
Find proteins for P31224 (Escherichia coli (strain K12))
Explore P31224 
Go to UniProtKB:  P31224
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP31224
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
DARPin
D, E
169synthetic constructMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.191 
  • R-Value Observed: 0.193 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 145.59α = 90
b = 161.59β = 90
c = 245.97γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2014-10-15 
  • Deposition Author(s): Pos, K.M.

Revision History  (Full details and data files)

  • Version 1.0: 2014-10-15
    Type: Initial release
  • Version 1.1: 2023-12-20
    Changes: Data collection, Database references, Derived calculations, Refinement description, Structure summary