4NSC

Crystal Structure of CBARA1 in the Apo-form

Summary for 4NSC

• Entry DOI: 10.2210/pdb4nsc/pdb
• Related: 4NSD
• Descriptor: Calcium uptake protein 1, mitochondrial (2 entities in total)
• Functional Keywords: ef-hand, calcium binding protein
• Biological source: Homo sapiens (human)
• Cellular location: Mitochondrion inner membrane; Peripheral membrane protein: Q9BPX6
• Total number of polymer chains: 6
• Total formula weight: 278057.88

Authors

Wang, L.,Yang, X.,Li, S.,Shen, Y. (deposition date: 2013-11-28, release date: 2014-02-26, Last modification date: 2024-02-28)

Primary citation

Wang, L.,Yang, X.,Li, S.,Wang, Z.,Liu, Y.,Feng, J.,Zhu, Y.,Shen, Y.
Structural and mechanistic insights into MICU1 regulation of mitochondrial calcium uptake.
Embo J., 33:594-604, 2014

PubMed Abstract: Mitochondrial calcium uptake is a critical event in various cellular activities. Two recently identified proteins, the mitochondrial Ca(2+) uniporter (MCU), which is the pore-forming subunit of a Ca(2+) channel, and mitochondrial calcium uptake 1 (MICU1), which is the regulator of MCU, are essential in this event. However, the molecular mechanism by which MICU1 regulates MCU remains elusive. In this study, we report the crystal structures of Ca(2+)-free and Ca(2+)-bound human MICU1. Our studies reveal that Ca(2+)-free MICU1 forms a hexamer that binds and inhibits MCU. Upon Ca(2+) binding, MICU1 undergoes large conformational changes, resulting in the formation of multiple oligomers to activate MCU. Furthermore, we demonstrate that the affinity of MICU1 for Ca(2+) is approximately 15-20 μM. Collectively, our results provide valuable details to decipher the molecular mechanism of MICU1 regulation of mitochondrial calcium uptake.

PubMed: 24514027
DOI: 10.1002/embj.201386523

Experimental method

X-RAY DIFFRACTION (3.2 Å)