Published on Thu Aug 05 2021

Principles of sensor-effector organization in six-transmembrane ion channels

Dou, A. K., Kang, P. W., Hou, P., Zaydman, M. A., Zheng, J., Jegla, T., Cui, J.

Receptor proteins sense stimuli and generate downstream signals via sensor and effector domains. Presently, the structural constraints on sensor-effector organization across receptor protein superfamilies are not clear. Comparisons to structural and functional studies reveal a conserved "core" sector.

3
1
2
Abstract

Receptor proteins sense stimuli and generate downstream signals via sensor and effector domains. Presently, the structural constraints on sensor-effector organization across receptor protein superfamilies are not clear. Here, we perform statistical coupling analysis (SCA) on the transient receptor potential (TRP) and voltage-gated potassium (Kv) ion channel superfamilies to characterize the networks of coevolving residues, or protein sectors, that mediate their receptor functions. Comparisons to structural and functional studies reveal a conserved "core" sector that extends from the pore and mediates effector functions, including pore gating and sensor-pore coupling, while sensors correspond to family-specific "accessory" sectors and localize according to three principles: Sensors (1) may emerge in any region with access to the core, (2) must maintain contact with the core, and (3) must preserve the integrity of the core. This sensor-core architecture may represent a conserved and generalizable paradigm for the structure-function relationships underlying the evolution of receptor proteins.