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Calcium Channelopathies: Structural Insights into Disorders of the Muscle Excitation–Contraction Complex

Authors
  • Pancaroglu, Raika
  • Van Petegem, Filip
Type
Published Article
Journal
Annual Review of Genetics
Publisher
Annual Reviews
Publication Date
Nov 23, 2018
Volume
52
Pages
373–396
Identifiers
DOI: 10.1146/annurev-genet-120417-031311
Source
Annual Reviews
Keywords
License
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Abstract

Ion channels are membrane proteins responsible for the passage of ions down their electrochemical gradients and across biological membranes. In this, they generate and shape action potentials and provide secondary messengers for various signaling pathways. They are often part of larger complexes containing auxiliary subunits and regulatory proteins. Channelopathies arise from mutations in the genes encoding ion channels or their associated proteins. Recent advances in cryo-electron microscopy have resulted in an explosion of ion channel structures in multiple states, generating a wealth of new information on channelopathies. Disease-associated mutations fall into different categories, interfering with ion permeation, protein folding, voltage sensing, ligand and protein binding, and allosteric modulation of channel gating. Prime examples of these are Ca2+-selective channels expressed in myocytes, for which multiple structures in distinct conformational states have recently been uncovered. We discuss the latest insights into these calcium channelopathies from a structural viewpoint.

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