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 n m to 130 n m . 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.