Posts Tagged ‘structure’

Activation mechanism of the calcium-activated chloride channel TMEM16A revealed by cryo-EM

The calcium-activated chloride channel TMEM16A is a ligand-gated anion channel that opens in response to an increase in intracellular Ca2+ concentration. The protein is broadly expressed and contributes to diverse physiological processes, including transepithelial chloride transport and the control of electrical signalling in smooth muscles and certain neurons. As a member of the TMEM16 (or anoctamin) family of membrane proteins, TMEM16A is closely related to paralogues that function as scramblases, which facilitate the bidirectional movement of lipids across membranes. The unusual functional diversity of the TMEM16 family and the relationship between two seemingly incompatible transport mechanisms has been the focus of recent investigations. Previous breakthroughs were obtained from the X-ray structure of the lipid scramblase of the fungus Nectria haematococca (nhTMEM16), and from the cryo-electron microscopy structure of mouse TMEM16A at 6.6 Å (ref. 14). Although the latter structure disclosed the architectural differences that distinguish ion channels from lipid scramblases, its low resolution did not permit a detailed molecular description of the protein or provide any insight into its activation by Ca2+. Here we describe the structures of mouse TMEM16A at high resolution in the presence and absence of Ca2+. These structures reveal the differences between ligand-bound and ligand-free states of a calcium-activated chloride channel, and when combined with functional experiments suggest a mechanism for gating. During activation, the binding of Ca2+ to a site located within the transmembrane domain, in the vicinity of the pore, alters the electrostatic properties of the ion conduction path and triggers a conformational rearrangement of an α-helix that comes into physical contact with the bound ligand, and thereby directly couples ligand binding and pore opening. Our study describes a process that is unique among channel proteins, but one that is presumably general for both functional branches of the TMEM16 family.

The quantization of space

Quantum mechanics defines our observable physical environment only in terms of the probabilistic values associated with Schrödinger’s wave equation. More specifically it defines a particle in terms of the instantaneous collapse of a wave function which it assumes extends form one edge of the universe to the other. Schrodinger Equation and Material Waves However this […]

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A Relativistic Quantum Mechanics

Quantum mechanistic defines our observable environment only in terms of the probabilistic values associated with Schrödinger’s wave equation. Many interpret this as meaning a particle and all other objects exists in a world of probabilities and only become connected to the environment when observed.  Additionally it assumes that a particle is distributed or simultaneous exists […]

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The quantum properties of non-point particles

Quantum theory: it’s unreal We know that everything in the universe including particles have physical size. Even so for the past 50 years, the Standard Model of particle physics which many say has given us the most complete mathematical description of the particles and forces that shape our world ignores this fact and treats them […]

The post The quantum properties of non-point particles appeared first on The Imagineer's Chronicles.

A relativistic Quantum Mechanics

Quantum mechanistic defines our observable environment only in terms of the probabilistic values associated with Schrödinger’s wave equation. Many interpret this as meaning a particle and all other objects exists in a world of probabilities and only become connected to the environment when observed.  Additionally it assumes that a particle is distributed or simultaneous exists […]

The post A relativistic Quantum Mechanics appeared first on The Imagineer's Chronicles.

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