Biology Reference
In-Depth Information
FIGURE 3.2
3D representation of the communities holding
4 nodes concerning dark (left) andMII (right)
states. Nodes are represented as spheres centered on the C
-atoms of the protein, on the C8
atom of retinal, and the O atom of the structural water molecules. Sphere diameter is
proportional to the number of links made by the node. Red, orange, yellow, and green refer to
the first, second, third, and fourth largest communities, respectively.
a
As for hubs, as already found by the PSN-MD approach coupled with me-
chanical unfolding simulations (
Fanelli & Seeber, 2010
), rhodopsin hubs crowd
in the retinal-binding site and involve both highly conserved amino acids and
ADRP mutation sites, the latter being localized essentially in the extracellular
half of the protein and in the N-term (
Fig. 3.4
). Remarkably, the number of
misfolding mutation sites behaving as hubs is higher in the inactive state than
theactiveone.Thisislikelylinkedto11-cis-retinalmakinganextendedcommu-
nity of nodes including ADRP mutation sites (
Figs. 3.2-3.4
). Another remarkable
difference between dark and MII states concerns the hub behavior of highly con-
served amino acids in the cytosolic regions. In particular, whereas the arginine of
the E/DRY motif and Y306 of the NPxxY motif are hubs in the dark state and not
in MII, the contrary happens for Y223 and F312, likely linked to the structural
rearrangements in the cytosolic regions following photoisomerization of 11-cis-
retinal. In general, in the dark state, hub specificity essentially locates in the
N-term, E2, and H7, whereas in MII, it essentially resides in H2, E2, and H5
(
Fig. 3.4
).
