Early studies on the lateral diffusion of rhodopsin in ROS membranes resulted in viewing this visual receptor as monomeric entity freely diffusing in a phospholipid bilayer (Calvert et al., 2001; Chabre et al., 2003; Liebman et al., 1982; Poo and Cone, 1974). However, it is important to stress that the movement of rhodopsin restricted to approximately two-dimensional environment of membranous phospholipid bilayer would rather reduce its dynamic freedom by orders of magnitude relative to soluble proteins. Such reduction in diffusion from three to two dimensional biological membranes most likely would stimulate receptors clustering even in cases of low affinity interactions. In fact, more thorough investigations on GPCRs oligomerization revealed
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These lipid rafts recruit fatty-acyl modified signaling proteins, increasing their effective concentration and affecting their function. Thus, such protein compartmentalization could be a universal mechanism for most adaptive cellular signal transduction (Simons k Toomre d 2000). In case of rhodopsin, visualization of this light receptor in the native ROS membranes by high resolution AFM indicated that it is not distributed evenly but rather localized into specific nanodomains, where it forms oligomeric arrays. Thus, the concept of rhodopsin existing as a freely mobile, monomeric entity had to be revised. In fact, in 2009 the reappraisal studies on the lateral diffusion of rhodopsin in amphibian and gecko rods using high-speed dichroic spectrophotometer confirmed an existence of a large fraction of immobile rhodopsin of different sizes in different discs (Govardovskii et al., …show more content…
In such scenario, activation energy could be lost if the neighboring rhodopsin, the one not associated with Gtα would be excited by a photon. However, this loss could be prevented if asymmetric rhodopsin activation exists. In fact, ligand induced allosteric modulation between receptor protomers within the dimer has been demonstrated for other GPCRs. Thus, conformational changes induced by a photon in the rhodopsin monomer that does not physically interact with Gtα would induce structural evolution towards Meta II active state in the Gtα-precoupled rhodopsin (Neri et al., 2010). Such mechanism would be critical to enhance efficiency of rhodopsin activation and potentially its desensitization. Membrane MD simulations of a rhodopsin dimer revealed that rhodopsin activation can occur in an asymmetric manner where structural changes occurring in the photoactivated rhodopsin stimulate conformational rearrangements in the neighboring, not activated rhodopsin involving disruption of an “ionic lock”, movement of helix TM3 and opening of the G-protein binding domain thus triggering an evolution toward the active Meta II state of rhodopsin. In support of such possibility cross-phosphorylation between activated and non-active receptor has been reported for several GPCRs including
These lipid rafts recruit fatty-acyl modified signaling proteins, increasing their effective concentration and affecting their function. Thus, such protein compartmentalization could be a universal mechanism for most adaptive cellular signal transduction (Simons k Toomre d 2000). In case of rhodopsin, visualization of this light receptor in the native ROS membranes by high resolution AFM indicated that it is not distributed evenly but rather localized into specific nanodomains, where it forms oligomeric arrays. Thus, the concept of rhodopsin existing as a freely mobile, monomeric entity had to be revised. In fact, in 2009 the reappraisal studies on the lateral diffusion of rhodopsin in amphibian and gecko rods using high-speed dichroic spectrophotometer confirmed an existence of a large fraction of immobile rhodopsin of different sizes in different discs (Govardovskii et al., …show more content…
In such scenario, activation energy could be lost if the neighboring rhodopsin, the one not associated with Gtα would be excited by a photon. However, this loss could be prevented if asymmetric rhodopsin activation exists. In fact, ligand induced allosteric modulation between receptor protomers within the dimer has been demonstrated for other GPCRs. Thus, conformational changes induced by a photon in the rhodopsin monomer that does not physically interact with Gtα would induce structural evolution towards Meta II active state in the Gtα-precoupled rhodopsin (Neri et al., 2010). Such mechanism would be critical to enhance efficiency of rhodopsin activation and potentially its desensitization. Membrane MD simulations of a rhodopsin dimer revealed that rhodopsin activation can occur in an asymmetric manner where structural changes occurring in the photoactivated rhodopsin stimulate conformational rearrangements in the neighboring, not activated rhodopsin involving disruption of an “ionic lock”, movement of helix TM3 and opening of the G-protein binding domain thus triggering an evolution toward the active Meta II state of rhodopsin. In support of such possibility cross-phosphorylation between activated and non-active receptor has been reported for several GPCRs including