Asset Details
Do you wish to reserve the book?
Structural mechanism of TRPM7 channel regulation by intracellular magnesium
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Structural mechanism of TRPM7 channel regulation by intracellular magnesium
Do you wish to request the book?
Structural mechanism of TRPM7 channel regulation by intracellular magnesium
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Structural mechanism of TRPM7 channel regulation by intracellular magnesium
2022
Overview
Zn
2+
, Mg
2+
and Ca
2+
are essential divalent cations implicated in many metabolic processes and signalling pathways. An emerging new paradigm is that the organismal balance of these cations predominantly depends on a common gatekeeper, the channel-kinase TRPM7. Despite extensive electrophysiological studies and recent cryo-EM analysis, an open question is how the channel activity of TRPM7 is activated. Here, we performed site-directed mutagenesis of mouse TRPM7 in conjunction with patch-clamp assessment of whole-cell and single-channel activity and molecular dynamics (MD) simulations to show that the side chains of conserved N1097 form an inter-subunit Mg
2+
regulatory site located in the lower channel gate of TRPM7. Our results suggest that intracellular Mg
2+
binds to this site and stabilizes the TRPM7 channel in the closed state, whereas the removal of Mg
2+
favours the opening of TRPM7. Hence, our study identifies the structural underpinnings through which the TRPM7 channel is controlled by cytosolic Mg
2+
, representing a new structure–function relationship not yet explored among TRPM channels.
Publisher
Springer International Publishing,Springer Nature B.V
Subject
/ Biomedical and Life Sciences
/ calcium
/ Cations
/ Cations, Divalent - metabolism
/ Kinases
/ Mice
/ Mutation
/ Original
/ Phosphotransferases - metabolism
/ Proteins
/ structure-activity relationships
/ Structure-function relationships
/ Transient receptor potential proteins
/ TRPM Cation Channels - genetics
/ TRPM Cation Channels - metabolism
/ Zinc
