1. J Phys Chem B. 2010 Dec 9;114(48):15948-57. Epub 2010 Nov 11.

Dynamics and structural changes induced by ATP binding in SAV1866, a bacterial
ABC exporter.

Becker JP, Van Bambeke F, Tulkens PM, Prévost M.

Structure et Fonction des Membranes Biologiques, Université Libre de Bruxelles,
Boulevard du Triomphe CP 206/2, B-1050 Brussels, Belgium.

Multidrug transporters of the ATP-binding cassette family export a wide variety
of compounds across membranes in both prokaryotes and eukaryotes, using ATP
hydrolysis as energy source. Several of these membrane proteins are of clinical
importance. Although biochemical and structural studies have provided insights
into the mechanism underlying substrate transport, many key questions subsist
regarding the molecular and structural nature of this mechanism. In particular,
the detailed conformational changes occurring during the catalytic cycle are
still elusive. We explored the conformational changes occurring upon ATP/Mg(2+)
binding using molecular dynamics simulations starting from the nucleotide-bound
structure of SAV1866 embedded in an explicit lipid bilayer. The removal of
nucleotide revealed a major rearrangement in the outer membrane leaflet portion
of the transmembrane domain (TMD) resulting in the closure of the central cavity 
at the extracellular side. This closure is similar to that observed in the
crystal nucleotide-free structures. The interface of the nucleotide-binding
domain dimer (NDB) is significantly more hydrated in the nucleotide-free
trajectory though it is not disrupted. This finding suggests that the TMD closure
could occur as a first step preceding the dissociation of the dimer. The
transmission pathway of the signal triggered by the removal of ATP/Mg(2+) mainly 
involves the conserved Q-loop and X-loop as well as TM6.


PMID: 21069970 [PubMed - in process]