Structure and function of the N-terminal domain of the human mitochondrial calcium uniporter

EMBO Reports
Youngjin LeeSoo Hyun Eom

Abstract

The mitochondrial calcium uniporter (MCU) is responsible for mitochondrial calcium uptake and homeostasis. It is also a target for the regulation of cellular anti-/pro-apoptosis and necrosis by several oncogenes and tumour suppressors. Herein, we report the crystal structure of the MCU N-terminal domain (NTD) at a resolution of 1.50 Å in a novel fold and the S92A MCU mutant at 2.75 Å resolution; the residue S92 is a predicted CaMKII phosphorylation site. The assembly of the mitochondrial calcium uniporter complex (uniplex) and the interaction with the MCU regulators such as the mitochondrial calcium uptake-1 and mitochondrial calcium uptake-2 proteins (MICU1 and MICU2) are not affected by the deletion of MCU NTD. However, the expression of the S92A mutant or a NTD deletion mutant failed to restore mitochondrial Ca(2+) uptake in a stable MCU knockdown HeLa cell line and exerted dominant-negative effects in the wild-type MCU-expressing cell line. These results suggest that the NTD of MCU is essential for the modulation of MCU function, although it does not affect the uniplex formation.

References

Jan 25, 1976·Journal of Molecular Biology·W KabschD Eisenberg
Jul 1, 1994·Physiological Reviews·T PozzanJ Meldolesi
Nov 15, 1961·Proceedings of the National Academy of Sciences of the United States of America·H F DELUCA, G W ENGSTROM
Jan 23, 2004·Nature·Yuriy KirichokDavid E Clapham
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Sep 20, 2006·The Journal of Cell Biology·György CsordásGyörgy Hajnóczky
Dec 21, 2006·The Journal of Cell Biology·György SzabadkaiRosario Rizzuto
Oct 16, 2007·Bioinformatics·Surendra S NegiWerner Braun
Oct 17, 2008·Physiological Reviews·Heping Cheng, W J Lederer
Oct 31, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·P GonnordJ M Kanellopoulos
Dec 5, 2008·Nature·Olga Martins de Brito, Luca Scorrano
Mar 14, 2009·Journal of Molecular and Cellular Cardiology·Jennifer Hom, Shey-Shing Sheu
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Jun 27, 2009·Science·Benoît KornmannPeter Walter
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Alexei Vagin, Alexei Teplyakov
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
May 12, 2010·Nucleic Acids Research·Liisa Holm, Päivi Rosenström
Aug 10, 2010·Nature·Fabiana PerocchiVamsi K Mootha
Oct 5, 2010·Biochimica Et Biophysica Acta·Kathleen W KinnallyLaurent M Dejean
Dec 9, 2010·Molecular & Cellular Proteomics : MCP·Jannie M R DanielsenMichael L Nielsen
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Martyn D WinnKeith S Wilson
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Garib N MurshudovAlexei A Vagin
Sep 10, 2011·Science·Yongxin ZhaoRobert E Campbell
Oct 25, 2011·Nature·Geert van den BogaartReinhard Jahn
Apr 7, 2012·Cell Calcium·Carlotta GiorgiPaolo Pinton
Oct 12, 2012·Nature·Mei-Ling A JoinerMark E Anderson
Oct 23, 2012·Nature Biotechnology·Jeffrey D MartellAlice Y Ting
Nov 28, 2012·Nature Cell Biology·Karthik MallilankaramanMuniswamy Madesh
Nov 30, 2012·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Junsen TongYoung Jun Im
Aug 15, 2013·Nature Communications·Julien PrudentGermain Gillet
Dec 3, 2013·Nucleic Acids Research·Antonina AndreevaAlexey G Murzin

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Citations

Mar 16, 2016·Proceedings of the National Academy of Sciences of the United States of America·Dipayan ChaudhuriDavid E Clapham
Feb 24, 2016·Biochimica Et Biophysica Acta·Jessica Matesanz-IsabelJavier Alvarez
Jun 13, 2016·European Biophysics Journal : EBJ·Roberta PeruzzoLuigi Leanza
May 6, 2016·Annual Review of Biochemistry·Diego De StefaniTullio Pozzan
Mar 24, 2016·Journal of Experimental Botany·Stephan WagnerIldikò Szabò
Aug 30, 2016·Cell Chemical Biology·Samuel K LeePeter B Stathopulos
Oct 4, 2016·Trends in Biochemical Sciences·Anna RaffaelloRosario Rizzuto
Apr 29, 2016·American Journal of Physiology. Cell Physiology·Bong Sook JhunJin O-Uchi
Dec 15, 2017·Journal of the Royal Society, Interface·B Rita AlevriadouMuniswamy Madesh
Sep 16, 2018·The Journal of Physiology·Pei WangShey-Shing Sheu
May 3, 2016·Nature·Kirill OxenoidJames J Chou
May 2, 2020·Electrophoresis·James P Barger, Patrick F Dillon
Mar 16, 2018·Pflügers Archiv : European journal of physiology·Cristina MammucariRosario Rizzuto
Jun 30, 2018·Science·Jiho YooSeok-Yong Lee
Jun 11, 2019·Oxidative Medicine and Cellular Longevity·Simona FenoAnna Raffaello
Apr 1, 2020·Frontiers in Plant Science·Lorella NavazioIldikò Szabò
Oct 2, 2019·International Journal of Molecular Sciences·Nadezhda V TarasovaAndrey V Elchaninov
Jul 12, 2018·Nature·Nam X NguyenYouxing Jiang
May 28, 2020·International Journal of Molecular Sciences·Megan NoblePeter B Stathopulos
Aug 10, 2020·Life Science Alliance·Melissa Js MacEwenYasemin Sancak
Jul 26, 2017·Frontiers in Oncology·Cristina MammucariRosario Rizzuto
Aug 26, 2018·Nature Reviews. Molecular Cell Biology·Carlotta GiorgiPaolo Pinton
Jul 12, 2018·Nature·Rozbeh BaradaranStephen Barstow Long
Dec 3, 2020·Cell Calcium·Simona FenoDenis Vecellio Reane
Oct 27, 2020·Current Opinion in Physiology·Edmund J CarvalhoMuniswamy Madesh
May 12, 2020·Journal of Molecular and Cellular Cardiology·Julia C Liu
Dec 24, 2019·Current Opinion in Chemical Biology·Joshua J Woods, Justin J Wilson
Dec 10, 2020·American Journal of Physiology. Cell Physiology·B Rita AlevriadouMuniswamy Madesh
Apr 4, 2021·International Journal of Molecular Sciences·Anna WeiserUmberto De Marchi
May 25, 2021·Frontiers in Cell and Developmental Biology·Yingzhen ZhangXiaoyun Liu
Sep 29, 2021·Cell Communication and Signaling : CCS·Tingting LiZhiyong Zeng
Oct 27, 2021·Physiological Reviews·Joanne F Garbincius, John W Elrod

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Methods Mentioned

BETA
ubiquitination
circular dichroism
electrophoresis
size exclusion chromatography
gel filtration

Software Mentioned

InterProSurf
MOLREP
CCP4
HKL2000
Protein – Protein Interaction Site Predictor (
Coot SSM superpose
‐ PPISP )
Refmac5
Coot
CCP4 suite

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