A supramolecular assembly of cone-specific G-protein and cryptochrome 4a on lipid bilayer

Signal transduction processes often involve membrane-associated proteins allowing facilitated diffusion of reactive partners in a phospholipid bilayer plane. A benchmark example is phototransduction, taking place at the disk membranes of vertebrate rod and cone outer segments. Long-wavelength sensitive cones in night migratory songbirds harbor another sensory signaling pathway. These birds can detect the Earth's magnetic field probably utilizing a radical-pair mechanism based on a photosensitive process in a cryptochrome protein. The isoform cryptochrome 4a in European robin is discussed as a prime magnetoreceptor candidate based on its photochemistry. However, cryptochrome 4a needs to have a fixed position on the membrane to operate as a magnetic field detector. We employed surface plasmon resonance to immobilize phospholipid bilayers on a sensor chip surface to investigate critical protein-lipid interaction processes. One possible interaction partner of ErCry4a is the myristoylated G-protein α-subunit from European robin cone cells. The G protein bound to lipid bilayers with moderate-to-high affinity, consistent with a combination of hydrophobic and electrostatic interactions. ErCry4a could also interact with a pure lipid bilayer, but also with bilayers that have the myristoylated G-protein α-subunit attached. Both binding processes occurred with small differences in affinities, displaying K_D values in a range from 51 nm to 130 nm. Our results point to the importance of the myristoyl group for the interaction process and agree with a model where Gtα molecules could diffuse to ErCry4a, forming a high affinity complex for downstream signaling in magnetoreception.