The crystal structure of the MJ0796 ATP-binding cassette. Implications for the structural consequences of ATP hydrolysis in the active site of an ABC transporter

Yu Ren Yuan, Saul Blecker, Oksana Martsinkevich, Linda Millen, Philip J. Thomas, John F. Hunt

Research output: Contribution to journalArticlepeer-review

221 Scopus citations

Abstract

The crystal structure of the MJ0796 ATP-binding cassette, a member of the o228/LolD transporter family, has been determined at 2.7-Å resolution with MgADP bound at its active site. Comparing this structure with that of the ATP-bound form of the HisP ATP-binding cassette (Hung, L. W., Wang, I. X., Nikaido, K., Liu, P. Q., Ames, G. F., and Kim, S. H. (1998) Nature 396, 703-707) shows a 5-Å withdrawal of a phylogenetically invariant glutamine residue from contact with the γ-phosphate of ATP in the active site. This glutamine is located in a protein segment that links the rigid F 1-type ATP-binding core of the enzyme to an ABC transporter-specific α-helical subdomain that moves substantially away from the active site in the MgADP-bound structure of MJ0796 compared with the ATP-bound structure of HisP. A similar conformational effect is observed in the MgADP-bound structure of MJ1267 (Karpowich, N., et al. (2001) Structure, in press), establishing the withdrawal of the glutamine and the coupled outward rotation of the α-helical subdomain as consistent consequences of γ-phosphate release from the active site of the transporter. Considering this subdomain movement in the context of a leading model for the physiological dimer of cassettes present in ABC transporters indicates that it produces a modest mechanical change that is likely to play a role in facilitating nueleotide exchange out of the ATPase active site. Finally, it is noteworthy that one of the intersubunit packing interactions in the MJ0796 crystal involves antiparallel β-type hydrogen bonding interactions between the outermost β-strands in the two core β-sheets, leading to their fusion into a single extended β-sheet, a type of structural interaction that has been proposed to play a role in mediating the aggregation of β-sheet-containing proteins.

Original languageEnglish (US)
Pages (from-to)32313-32321
Number of pages9
JournalJournal of Biological Chemistry
Volume276
Issue number34
DOIs
StatePublished - Aug 24 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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