Science, Space and Technology News 2024
Adjacent cells freely exchange small molecules and ions with each other through channels made from proteins called connexins. Dysfunction in this important type of intercellular communication has been linked to a variety of diseases, including those of the heart and peripheral nervous system. Thus, connexins are important drug targets. Credit: Laura Canil
Adjacent cells can communicate directly through relatively large channels called gap junctions, which allow cells to freely exchange small molecules and ions with each other or with the outside environment. In this way, they can coordinate activities in the tissues or organs that they compose and maintain homeostasis.
As a result, the search is on for drugs that target connexins. Yet, understanding of the structure of connexins and how drugs bind to connexin channels to block or activate them is limited. Indeed, of the twenty-one types of connexins known to exist in humans, few of them are currently evaluated as drug targets.Now, researchers from PSI, ETH Zurich, and the University of Geneva have deepened our understanding of connexin channels and how they bind to drug molecules.
Computer simulations by collaborators at the University of Geneva helped the team understand the effect that mefloquine binding would have on the ability of the channel to permit ions to through. In this way, they showed that binding of the drug restricts the flow of solutes through the channel.The researchers hope that this new structural knowledge will be a starting point for developing new drugs with greater specificity for particular connexin channels.
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