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TitleStructural insights into the Ca-dependent gating of the human mitochondrial calcium uniporter.
Journal, issue, pagesElife, Vol. 9, Year 2020
Publish dateAug 7, 2020
AuthorsYan Wang / Yan Han / Ji She / Nam X Nguyen / Vamsi K Mootha / Xiao-Chen Bai / Youxing Jiang /
PubMed AbstractMitochondrial Ca uptake is mediated by an inner mitochondrial membrane protein called the mitochondrial calcium uniporter. In humans, the uniporter functions as a holocomplex consisting of MCU, EMRE, ...Mitochondrial Ca uptake is mediated by an inner mitochondrial membrane protein called the mitochondrial calcium uniporter. In humans, the uniporter functions as a holocomplex consisting of MCU, EMRE, MICU1 and MICU2, among which MCU and EMRE form a subcomplex and function as the conductive channel while MICU1 and MICU2 are EF-hand proteins that regulate the channel activity in a Ca-dependent manner. Here, we present the EM structures of the human mitochondrial calcium uniporter holocomplex (uniplex) in the presence and absence of Ca, revealing distinct Ca dependent assembly of the uniplex. Our structural observations suggest that Ca changes the dimerization interaction between MICU1 and MICU2, which in turn determines how the MICU1-MICU2 subcomplex interacts with the MCU-EMRE channel and, consequently, changes the distribution of the uniplex assemblies between the blocked and unblocked states.
External linksElife / PubMed:32762847 / PubMed Central
MethodsEM (single particle)
Resolution4.17 - 7.0 Å
Structure data

EMDB-22213:
Calcium channel
Method: EM (single particle) / Resolution: 4.5 Å

EMDB-22214:
Calcium channel
Method: EM (single particle) / Resolution: 7.0 Å

22215

6xjv

EMDB-22215, PDB-6xjv:
MCU holocomplex in High-calcium state
Method: EM (single particle) / Resolution: 4.17 Å

22216

6xjx

EMDB-22216, PDB-6xjx:
MCU holocomplex in Low-calcium blocking state
Method: EM (single particle) / Resolution: 4.6 Å

Source
  • homo sapiens (human)
KeywordsTRANSPORT PROTEIN / ion channel

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