The conformational cycle of a prototypical voltage-gated sodium channel.

Nature Chemical Biology
William A CatterallNing Zheng

Abstract

Electrical signaling was a dramatic development in evolution, allowing complex single-cell organisms like Paramecium to coordinate movement and early metazoans like worms and jellyfish to send regulatory signals rapidly over increasing distances. But how are electrical signals generated in biology? In fact, voltage-gated sodium channels conduct sodium currents that initiate electrical signals in all kingdoms of life, from bacteria to man. They are responsible for generating the action potential in vertebrate nerve and muscle, neuroendocrine cells, and other cell types1,2. Because of the high level of conservation of their core structure, it is likely that their fundamental mechanisms of action are conserved as well. Here we describe the complete cycle of conformational changes that a bacterial sodium channel undergoes as it transitions from resting to activated/open and inactivated/closed states, based on high-resolution structural studies of a single sodium channel. We further relate this conformational cycle of the ancestral sodium channel to the function of its vertebrate orthologs. The strong conservation of amino acid sequence and three-dimensional structure suggests that this model, at a fundamental level, is relevant for...Continue Reading

References

Jan 1, 1986·Annual Review of Biochemistry·W A Catterall
Jan 1, 1986·Annals of the New York Academy of Sciences·S Numa, M Noda
Feb 17, 1984·Science·W A Catterall
Dec 18, 2001·Science·D RenD E Clapham
Oct 31, 2002·The Journal of General Physiology·Baron Chanda, Francisco Bezanilla
Apr 26, 2005·Biophysical Journal·Evgeny PavlovRobert J French
Apr 3, 2010·Science·Xiao TaoRoderick MacKinnon
Jul 12, 2011·Nature·Jian PayandehWilliam A Catterall
Dec 14, 2011·Proceedings of the National Academy of Sciences of the United States of America·Vladimir Yarov-YarovoyWilliam A Catterall
Jun 28, 2013·Proceedings of the National Academy of Sciences of the United States of America·Nilmadhab ChakrabartiRégis Pomès
Jul 17, 2013·The Journal of General Physiology·Deborah L CapesBaron Chanda
Nov 26, 2013·Nature·Lin TangWilliam A Catterall
Aug 20, 2014·Proceedings of the National Academy of Sciences of the United States of America·Céline BoiteuxToby W Allen
May 14, 2016·Molecular Pharmaceutics·Christian JorgensenCarmen Domene
Mar 30, 2017·Proceedings of the National Academy of Sciences of the United States of America·Michael J LenaeusWilliam A Catterall
Apr 14, 2017·Nature Chemical Biology·William A CatterallNing Zheng
Dec 5, 2018·The Journal of General Physiology·Tamer M Gamal El-DinWilliam A Catterall
Dec 7, 2018·Proceedings of the National Academy of Sciences of the United States of America·Tamer M Gamal El-DinWilliam A Catterall
Feb 8, 2019·Proceedings of the National Academy of Sciences of the United States of America·Phuong T NguyenVladimir Yarov-Yarovoy
Jul 30, 2019·Cell·Goragot WisedchaisriWilliam A Catterall
Dec 24, 2019·Cell·Daohua JiangWilliam A Catterall

❮ Previous
Next ❯

Citations

Mar 7, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Beata NiklasWieslaw Nowak
Aug 24, 2021·ACS Pharmacology & Translational Science·Anne-Sophie DepuydtJan Tytgat

❮ Previous
Next ❯

Methods Mentioned

BETA
X-ray

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.