Lipid bilayers determine the allostery but not intrinsic affinity of cAMP binding to pacemaker channels.

In the human heart, the binding of cyclic adenosine monophosphate (cAMP), a second messenger, to hyperpolarization and cyclic nucleotide-gated (HCN) regulates the automaticity of pacemaker cells. Recent single-molecule binding studies show that cAMP bound to each subunit of purified tetrameric HCN channels independently, in contrast to findings in cells. To explore the lipid membrane's role in cAMP regulation, we reconstituted purified human HCN channels in various lipid nanodiscs and resolved single molecule ligand-binding dynamics.

Compressive-force induced activation of apo-calmodulin in protein signalling.

Mechanical force plays a critical role in the relationship between protein structure and function. Force manipulation by Atomic Force Microscope can be significant and trigger chemical and biological activities of proteins. Previously we have reported that Apo-CaM undergoes through a spontaneous tertiary structural rupture under a piconewton compressive force.