scholarly journals Correlation between structure and function in phosphatidylinositol lipid-dependent Kir2.2 gating

2021 ◽  
Author(s):  
Yuxi Zhang ◽  
Xiao Tao ◽  
Roderick MacKinnon
Keyword(s):  
Plasma Membrane ◽  
Lipid Bilayers ◽  
Structure And Function ◽  
Inward Rectifier ◽  
Burst Duration ◽  
Planar Lipid Bilayers ◽  
Kir Channels ◽  
Atomic Structures ◽  
Pore Opening ◽  
And Function

AbstractInward rectifier K+(Kir) channels regulate cell membrane potential. Different Kir channels respond to unique ligands, but all are regulated by phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). Using planar lipid bilayers we show that Kir2.2 exhibits bursts of openings separated by long quiescent inter-burst periods. Increasing PI(4,5)P2 concentration shortens the Kir2.2 inter-burst duration and lengthens the burst duration without affecting dwell times within a burst. From this, we propose that burst and inter-burst durations correspond to the CTD-docked and CTD-undocked conformations observed in the presence and absence of PI(4,5)P2 in atomic structures. We also studied the effect of different phosphatidylinositol lipids on Kir2.2 activation and conclude that the 5’ phosphate is essential to Kir2.2 pore opening. Other phosphatidylinositol lipids can compete with PI(4,5)P2 but cannot activate Kir2.2 without the 5’ phosphate. PI(4)P, which is directly interconvertible to and from PI(4,5)P2, might thus be a regulator of Kir channels in the plasma membrane.

Cellular structure and function

2021 ◽  
pp. 1-104
Keyword(s):  
Plasma Membrane ◽  
Nucleic Acids ◽  
Cellular Structure ◽  
Structure And Function ◽  
The Body ◽  
Signalling Pathways ◽  
Cellular Functions ◽  
Pharmacological Agents ◽  
Intracellular Organelles ◽  
And Function

‘Cellular structure and function’ covers the roles, structures, and functions of the main four types of macromolecules of the human body, namely proteins, lipids, carbohydrates, and nucleic acids. For these macromolecules, the roles and types of each class are discussed (for proteins this includes their roles as structural proteins and enzymes and their kinetics; for lipids, the roles and types of lipid found in the body are considered; for carbohydrates, their roles including structural and metabolic are discussed; and the structure of nucleic acids is described). Then follows a description of the organization of the cell, including the plasma membrane and its components, and the intracellular organelles. Cell growth, division, and apoptosis are covered, as are the formation of gametes, and finally the principles of how cellular functions can be modulated by pharmacological agents through receptors and signalling pathways are discussed.

scholarly journals ENaC structure and function in the wake of a resolved structure of a family member

2011 ◽  
Vol 301 (4) ◽  
pp. F684-F696 ◽  
Author(s):  
Ossama B. Kashlan ◽  
Thomas R. Kleyman
Keyword(s):  
Plasma Membrane ◽  
Ion Channel ◽  
Functional Data ◽  
Ion Selectivity ◽  
External Environment ◽  
Structure And Function ◽  
Close Proximity ◽  
Channel Assembly ◽  
And Function ◽  
Insight Into

Our understanding of epithelial Na+ channel (ENaC) structure and function has been profoundly impacted by the resolved structure of the homologous acid-sensing ion channel 1 (ASIC1). The structure of the extracellular and pore regions provide insight into channel assembly, processing, and the ability of these channels to sense the external environment. The absence of intracellular structures precludes insight into important interactions with intracellular factors that regulate trafficking and function. The primary sequences of ASIC1 and ENaC subunits are well conserved within the regions that are within or in close proximity to the plasma membrane, but poorly conserved in peripheral domains that may functionally differentiate family members. This review examines functional data, including ion selectivity, gating, and amiloride block, in light of the resolved ASIC1 structure.

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