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Figure 5.
Fig. 5. Summary of conformational changes in MsbA. (A)
Conformational changes within the MsbA dimer alter the
accessibility to the internal chamber from inward to outward
facing. For clarity, only TM helices (labeled 1–6) of one
monomer (cyan) are shown inside a surface rendering of the
dimer. The open and closed apo conformations form an
inward-facing V between TM4/TM5 and TM3/TM6 (red asterisk). The
nucleotide-bound conformation (MsbA-AMPPNP) forms an
outward-facing V between TM3/TM6 and TM1/TM2, just above the
elbow helix (black asterisk). Upon nucleotide binding,
TM4/TM5/IH2 moves, causing TM3/TM6 to split away from TM1/TM2,
which results in an outward-facing conformation. Both inward-
and outward-facing conformations are mediated by intramolecular
interactions within a single monomer, but by different sets of
helices. (B) Simplified cartoon model illustrating the points
above. The relative position of each TM helix is labeled with a
number (one monomer in white and the other in gray). The arrows
illustrate the motions required to go to the next state. (C)
Top-down view of NBDs (one monomer shown in white and the other
in gray). IH1 (green) and IH2 (yellow) from both monomers are
shown. In the absence of nucleotide (apo), the NBDs are in
similar orientations with the ATP-binding half-sites (LSGGQ and
P-loop) facing each other; the P-loops (red) are roughly aligned
(dashed lines) with one another across the dimer interface. Upon
nucleotide binding (AMPPNP - magenta), the canonical ATP
sandwich is formed, aligning the nucleotide between the LSGGQ
and P-loop. IH1 tracks with the cis-monomer, whereas IH2 tracks
with the trans-monomer. The motion of the NBDs from closed-apo-
to nucleotide-bound transmits a structural change (described
above) to the TMs via IH1 and IH2, resulting in an
outward-facing conformation.
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