Principles underlying energetic coupling along an allosteric communication trajectory of a voltage-activated K+ channel.
The information flow between distal elements of a protein may rely on allosteric communication trajectories lying along the protein's tertiary or quaternary structure. To unravel the underlying features of energy parsing along allosteric pathways in voltage-gated K(+) channels, high-order thermodynamic coupling analysis was performed. We report that such allosteric trajectories are functionally conserved and delineated by well defined boundaries. Moreover, allosteric trajectories assume a hierarchical organization whereby increasingly stronger layers of cooperative residue interactions act to ensure efficient and cooperative long-range coupling between distal channel regions. Such long-range communication is brought about by a coupling of local and global conformational changes, suggesting that the allosteric trajectory also corresponds to a pathway of physical deformation. Supported by theoretical analyses and analogy to studies analyzing the contribution of long-range residue coupling to protein stability, we propose that such experimentally derived trajectory features are a general property of allosterically regulated proteins.
Sadovsky
Evgeniya
E
Department of Life Sciences and Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel.
Yifrach
Ofer
O
D000494:Allosteric Regulation / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology*; D008954:Models, Biological; D017434:Protein Structure, Tertiary; D051637:Shaker Superfamily of Potassium Channels / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D013816:Thermodynamics
D051637:Shaker Superfamily of Potassium Channels