Gunjan Dixit1, Carole Dabney-Smith1, Gary A Lorigan2. 1. Cell, Molecular, and Structural Biology Program, Department of Chemistry & Biochemistry, Miami University, Oxford, OH 45056, USA; Department of Chemistry and Biochemistry, Miami University, Oxford, OH 45056, USA. 2. Cell, Molecular, and Structural Biology Program, Department of Chemistry & Biochemistry, Miami University, Oxford, OH 45056, USA; Department of Chemistry and Biochemistry, Miami University, Oxford, OH 45056, USA. Electronic address: gary.lorigan@miamioh.edu.
Abstract
BACKGROUND: Ion channels play crucial roles in cellular biology, physiology, and communication including sensory perception. Voltage-gated potassium (Kv) channels execute their function by sensor activation, pore-coupling, and pore opening leading to K+ conductance. SCOPE OF REVIEW: This review focuses on a voltage-gated K+ ion channel KCNQ1 (Kv 7.1). Firstly, discussing its positioning in the human ion chanome, and the role of KCNQ1 in the multitude of cellular processes. Next, we discuss the overall channel architecture and current structural insights on KCNQ1. Finally, the gating mechanism involving members of the KCNE family and its interaction with non-KCNE partners. MAJOR CONCLUSIONS: KCNQ1 executes its important physiological functions via interacting with KCNE1 and non-KCNE1 proteins/molecules: calmodulin, PIP2, PKA. Although, KCNQ1 has been studied in great detail, several aspects of the channel structure and function still remain unexplored. This review emphasizes the structural and biophysical studies of KCNQ1, its interaction with KCNE1 and non-KCNE1 proteins and focuses on several seminal findings showing the role of VSD and the pore domain in the channel activation and gating properties. GENERAL SIGNIFICANCE: KCNQ1 mutations can result in channel defects and lead to several diseases including atrial fibrillation and long QT syndrome. Therefore, a thorough structure-function understanding of this channel complex is essential to understand its role in both normal and disease biology. Moreover, unraveling the molecular mechanisms underlying the regulation of this channel complex will help to find therapeutic strategies for several diseases.
BACKGROUND: Ion channels play crucial roles in cellular biology, physiology, and communication including sensory perception. Voltage-gated potassium (Kv) channels execute their function by sensor activation, pore-coupling, and pore opening leading to K+ conductance. SCOPE OF REVIEW: This review focuses on a voltage-gated K+ ion channel KCNQ1 (Kv 7.1). Firstly, discussing its positioning in the human ion chanome, and the role of KCNQ1 in the multitude of cellular processes. Next, we discuss the overall channel architecture and current structural insights on KCNQ1. Finally, the gating mechanism involving members of the KCNE family and its interaction with non-KCNE partners. MAJOR CONCLUSIONS:KCNQ1 executes its important physiological functions via interacting with KCNE1 and non-KCNE1 proteins/molecules: calmodulin, PIP2, PKA. Although, KCNQ1 has been studied in great detail, several aspects of the channel structure and function still remain unexplored. This review emphasizes the structural and biophysical studies of KCNQ1, its interaction with KCNE1 and non-KCNE1 proteins and focuses on several seminal findings showing the role of VSD and the pore domain in the channel activation and gating properties. GENERAL SIGNIFICANCE: KCNQ1 mutations can result in channel defects and lead to several diseases including atrial fibrillation and long QT syndrome. Therefore, a thorough structure-function understanding of this channel complex is essential to understand its role in both normal and disease biology. Moreover, unraveling the molecular mechanisms underlying the regulation of this channel complex will help to find therapeutic strategies for several diseases.
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