PDBsum entry 6iih

Calcium binding protein

PDB id: 6iih

Contents

Protein chains

446 a.a.

Metals

_CA ×3

Waters ×819

PDB id:

6iih

Name:

Calcium binding protein

Title:

Crystal structure of mitochondrial calcium uptake 2(micu2)

Structure:

Endolysin,calcium uptake protein 2, mitochondrial. Chain: a, b. Synonym: lysis protein,lysozyme,muramidase,ef-hand domain-containing family member a1. Engineered: yes. Mutation: yes

Source:

Enterobacteria phage t4, homo sapiens. Bacteriophage t4, human. Organism_taxid: 10665, 9606. Gene: micu2, efha1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.96Å R-factor: 0.181 R-free: 0.227

Authors:

Q.Shen,W.Wu,J.Zheng,Z.Jia

Key ref:

W.Wu et al. (2019). The crystal structure of MICU2 provides insight into Ca²⁺ binding and MICU1-MICU2 heterodimer formation. EMBO Rep, 20, e47488. PubMed id: 31397067 DOI: 10.15252/embr.201847488

Date:

06-Oct-18 Release date: 14-Aug-19

Protein chains

P00720  (ENLYS_BPT4) -  Endolysin from Enterobacteria phage T4

Seq: 164 a.a.

Struc: 446 a.a.*

Protein chains

Q8IYU8  (MICU2_HUMAN) -  Calcium uptake protein 2, mitochondrial from Homo sapiens

Seq: 434 a.a.

Struc: 446 a.a.*

* PDB and UniProt seqs differ at 84 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.2.1.17 - lysozyme.
• Reaction: Hydrolysis of the 1,4-beta-linkages between N-acetyl-D-glucosamine and N-acetylmuramic acid in peptidoglycan heteropolymers of the prokaryotes cell walls.

DOI no: 10.15252/embr.201847488

EMBO Rep 20:e47488 (2019)

PubMed id: 31397067

The crystal structure of MICU2 provides insight into Ca²⁺ binding and MICU1-MICU2 heterodimer formation.

W.Wu, Q.Shen, Z.Lei, Z.Qiu, D.Li, H.Pei, J.Zheng, Z.Jia.

ABSTRACT

The mitochondrial calcium uniporter (MCU) complex mediates the uptake of Ca²⁺ into mitochondria. Its activity is regulated by a heterodimer of MICU1 and MICU2, two EF-hand-containing proteins that act as the main gatekeeper of the uniporter. Herein we report the crystal structure of human MICU2 at 1.96 Å resolution. Our structure reveals a dimeric architecture of MICU2, in which each monomer adopts the canonical two-lobe structure with a pair of EF-hands in each lobe. Both Ca²⁺ -bound and Ca²⁺ -free EF-hands are observed in our structure. Moreover, we characterize the interaction sites within the MICU2 homodimer, as well as the MICU1-MICU2 heterodimer in both Ca²⁺ -free and Ca²⁺ -bound conditions. Glu242 in MICU1 and Arg352 in MICU2 are crucial for apo heterodimer formation, while Phe383 in MICU1 and Glu196 in MICU2 significantly contribute to the interaction in the Ca²⁺ -bound state. Based on our structural and biochemical analyses, we propose a model for MICU1-MICU2 heterodimer formation and its conformational transition from apo to a more compact Ca²⁺ -bound state, which expands our understanding of this co-regulatory mechanism critical for MCU's mitochondrial calcium uptake function.