Crystal structures of the MJ1267 ATP binding cassette reveal an induced-fit effect at the ATPase active site of an ABC transporter

Structure. 2001 Jul 3;9(7):571-86. doi: 10.1016/s0969-2126(01)00617-7.


Background: ATP binding cassette (ABC) transporters are ubiquitously distributed transmembrane solute pumps that play a causative role in numerous diseases. Previous structures have defined the fold of the ABC and established the flexibility of its alpha-helical subdomain. But the nature of the mechanical changes that occur at each step of the chemical ATPase cycle have not been defined.

Results: Crystal structures were determined of the MJ1267 ABC from Methanococcus jannaschii in Mg-ADP-bound and nucleotide-free forms. Comparison of these structures reveals an induced-fit effect at the active site likely to be a consequence of nucleotide binding. In the Mg-ADP-bound structure, the loop following the Walker B moves toward the Walker A (P-loop) coupled to backbone conformational changes in the intervening "H-loop", which contains an invariant histidine. These changes affect the region believed to mediate intercassette interaction in the ABC transporter complex. Comparison of the Mg-ADP-bound structure of MJ1267 to the ATP-bound structure of HisP suggests that an outward rotation of the alpha-helical subdomain is coupled to the loss of a molecular contact between the gamma-phosphate of ATP and an invariant glutamine in a segment connecting this subdomain to the core of the cassette.

Conclusions: The induced-fit effect and rotation of the alpha-helical subdomain may play a role in controlling the nucleotide-dependent change in cassette-cassette interaction affinity believed to represent the power-stroke of ABC transporters. Outward rotation of the alpha-helical subdomain also likely facilitates Mg-ADP release after hydrolysis. The MJ1267 structures therefore define features of the nucleotide-dependent conformational changes that drive transmembrane transport in ABC transporters.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP-Binding Cassette Transporters / chemistry*
  • ATP-Binding Cassette Transporters / metabolism*
  • Adenosine Triphosphate / metabolism*
  • Amino Acid Sequence
  • Amino Acid Transport Systems, Basic*
  • Bacterial Proteins*
  • Binding Sites
  • Catalytic Domain
  • Conserved Sequence
  • Crystallography, X-Ray
  • Magnesium / metabolism
  • Membrane Transport Proteins / chemistry
  • Membrane Transport Proteins / metabolism
  • Methanococcus / chemistry
  • Methanococcus / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Phosphates / metabolism
  • Phylogeny
  • Protein Conformation


  • ATP-Binding Cassette Transporters
  • Amino Acid Transport Systems, Basic
  • Bacterial Proteins
  • Membrane Transport Proteins
  • Phosphates
  • histidine permease, Bacteria
  • Adenosine Triphosphate
  • Magnesium

Associated data

  • PDB/1G6H
  • PDB/1GAJ