Posts Tagged ‘functional’

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.

How babies learn to walk holds potential clues to autism

“Our findings may allow us to identify the brain regions and networks that can predict aspects of autism before it’s possible to make a clinical diagnosis.”

Meshing, Geometric Modeling and Numerical Simulation 1: Form Functions, Triangulations and Geometric Modeling

  Triangulations, and more precisely meshes, are at the heart of many problems relating to a wide variety of scientific disciplines, and in particular numerical simulations of all kinds of physical phenomena. In numerical simulations, the …

Biomineralization-related specialization of hemocytes and mantle tissues of the Pacific oysters Crassostrea gigas [RESEARCH ARTICLE]

Anna V. Ivanina, Halina I. Falfushynska, Elia Beniash, Helen Piontkivska, and Inna M. SokolovaMolluscan exoskeleton (shell) plays multiple important roles including structural support, protection from predators and stressors, and physiological homeost…

New device lets paralyzed man move his arm with just his thoughts

A paralyzed 56-year-old Cleveland man has purportedly become the first person ever to regain the use of his hand and arm with the assistance of a brain-computer interface, according to new led by doctors from Case Western Reserve University and two Ohio-based hospitals. The patient’s name is Bill Kochevar, and according to NPR, he was […]

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