37250061
Structure of the ABC Transporter MsbA in Complex with ADP·Vanadate and Lipopolysaccharide
Select members of the adenosine triphosphate (ATP)-binding cassette (ABC) transporter family couple ATP binding and hydrolysis to substrate efflux and confer multidrug resistance. We have determined the x-ray structure of MsbA in complex with magnesium, adenosine diphosphate, and inorganic vanadate (Mg·ADP·Vi) and the rough-chemotype lipopolysaccharide, Ra LPS. The structure supports a model involving a rigid-body torque of the two transmembrane domains during ATP hydrolysis and suggests a mechanism by which the nucleotide-binding domain communicates with the transmembrane domain. We propose a lipid “flip-flop” mechanism in which the sugar groups are sequestered in the chamber while the hydrophobic tails are dragged through the lipid bilayer.
36922503
Flexibility in the ABC transporter MsbA: Alternating access with a twist
ATP-binding cassette (ABC) transporters are integral membrane proteins that translocate a wide variety of substrates across cellular membranes and are conserved from bacteria to humans. Here we compare four x-ray structures of the bacterial ABC lipid flippase, MsbA, trapped in different conformations, two nucleotide-bound structures and two in the absence of nucleotide. Comparison of the nucleotide-free conformations of MsbA reveals a flexible hinge formed by extracellular loops 2 and 3. This hinge allows the nucleotide-binding domains to disassociate while the ATP-binding half sites remain facing each other. The binding of the nucleotide causes a packing rearrangement of the transmembrane helices and changes the accessibility of the transporter from cytoplasmic (inward) facing to extracellular (outward) facing. The inward and outward openings are mediated by two different sets of transmembrane helix interactions. Altogether, the conformational changes between these structures suggest that large ranges of motion may be required for substrate transport.
119207714
Microcausality and quantization of the fermionic Myers–Pospelov model
We study the fermionic sector of the Myers and Pospelov theory with a general background n. The spacelike case without temporal component is well defined and no new ingredients came about, apart from the explicit Lorentz invariance violation. The lightlike case is ill defined and physically discarded. However, the other case where a nonvanishing temporal component of the background is present, the theory is physically consistent. We show that new modes appear as a consequence of higher time derivatives. We quantize the timelike theory and calculate the microcausality violation which turns out to occur near the light cone.
118127154
Unitarity, ghosts and nonminimal terms in Lorentz violating QED
The unitarity of a Lorentz-invariance violating QED model with higher-order Myers and Pospelov photons coupled to standard fermions is studied. As expected, we find ghost states associated to the higher-order terms that may lead to the loss of unitarity. An explicit calculation to check perturbative unitarity in the process of electron-positron scattering is performed and it is found to be possible to be preserved.