6XJV

MCU holocomplex in High-calcium state

Summary for 6XJV

• Entry DOI: 10.2210/pdb6xjv/pdb
• EMDB information: 22215
• Descriptor: Calcium uniporter protein, mitochondrial, Essential MCU regulator, mitochondrial, Calcium uptake protein 1, mitochondrial, ... (4 entities in total)
• Functional Keywords: ion channel, transport protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 20
• Total formula weight: 619348.54

Authors

Wang, Y.,Jiang, Y. (deposition date: 2020-06-24, release date: 2020-09-09, Last modification date: 2024-03-06)

Primary citation

Wang, Y.,Han, Y.,She, J.,Nguyen, N.X.,Mootha, V.K.,Bai, X.C.,Jiang, Y.
Structural insights into the Ca 2+ -dependent gating of the human mitochondrial calcium uniporter.
Elife, 9:-, 2020

PubMed Abstract: 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.

PubMed: 32762847
DOI: 10.7554/eLife.60513

Experimental method

ELECTRON MICROSCOPY (4.17 Å)