Crystal structure of MICU2 and comparison with MICU1 reveal insights into the uniporter gating mechanism.

Abstract:

:The mitochondrial uniporter is a Ca2+-channel complex resident within the organelle's inner membrane. In mammalian cells the uniporter's activity is regulated by Ca2+ due to concerted action of MICU1 and MICU2, two paralogous, but functionally distinct, EF-hand Ca2+-binding proteins. Here we present the X-ray structure of the apo form of Mus musculus MICU2 at 2.5-Å resolution. The core structure of MICU2 is very similar to that of MICU1. It consists of two lobes, each containing one canonical Ca2+-binding EF-hand (EF1, EF4) and one structural EF-hand (EF2, EF3). Two molecules of MICU2 form a symmetrical dimer stabilized by highly conserved hydrophobic contacts between exposed residues of EF1 of one monomer and EF3 of another. Similar interactions stabilize MICU1 dimers, allowing exchange between homo- and heterodimers. The tight EF1-EF3 interface likely accounts for the structural and functional coupling between the Ca2+-binding sites in MICU1, MICU2, and their complex that leads to the previously reported Ca2+-binding cooperativity and dominant negative effect of mutation of the Ca2+-binding sites in either protein. The N- and C-terminal segments of the two proteins are distinctly different. In MICU2 the C-terminal helix is significantly longer than in MICU1, and it adopts a more rigid structure. MICU2's C-terminal helix is dispensable in vitro for its interaction with MICU1 but required for MICU2's function in cells. We propose that in the MICU1-MICU2 oligomeric complex the C-terminal helices of both proteins form a central semiautonomous assembly which contributes to the gating mechanism of the uniporter.

authors

Kamer KJ,Jiang W,Kaushik VK,Mootha VK,Grabarek Z

doi

10.1073/pnas.1817759116

subject

Has Abstract

pub_date

2019-02-26 00:00:00

pages

3546-3555

issue

9

eissn

0027-8424

issn

1091-6490

pii

1817759116

journal_volume

116

pub_type

杂志文章
  • Rediscovery of the nucleolinus, a dynamic RNA-rich organelle associated with the nucleolus, spindle, and centrosomes.

    abstract::The nucleolinus is an RNA-rich compartment, closely apposed to or embedded within the nucleolus. Discovered over 150 y ago, fewer than two dozen articles have been published on the nucleolinus, probably because complex histochemical stains are required for its visualization in the great majority of cells. The nucleoli...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1008469107

    authors: Alliegro MA,Henry JJ,Alliegro MC

    更新日期:2010-08-03 00:00:00

  • Squid Pax-6 and eye development.

    abstract::Pax-6 in vertebrates and its homolog eyeless in Drosophila are known to be essential for eye development. Here we investigate the role of Pax-6 in eye development in another major systematic group, molluscs. We demonstrate that alternatively spliced RNAs derived from a single Pax-6 gene in the squid (Loligo opalescens...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.6.2421

    authors: Tomarev SI,Callaerts P,Kos L,Zinovieva R,Halder G,Gehring W,Piatigorsky J

    更新日期:1997-03-18 00:00:00

  • Inverted repeat structure of the Sry locus in mice.

    abstract::The testis-determining gene Sry is located on the short arm of the mouse Y chromosome in a region known to have undergone duplications and rearrangements in comparison with the equivalent portion of the human Y chromosome. Detailed analysis of the Sry genomic locus reveals a further difference in that the mouse Sry op...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.17.7953

    authors: Gubbay J,Vivian N,Economou A,Jackson D,Goodfellow P,Lovell-Badge R

    更新日期:1992-09-01 00:00:00

  • Relationship between in vivo degradative rates and isoelectric points of proteins.

    abstract::Previous studies have shown that in mammalian cells proteins of large molecular weight are degraded more rapidly than small ones. Evidence is presented here that half-lives of proteins are also related to their isoelectric points. A double-isotope method was used to compare degradative rates of soluble proteins separa...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.10.3893

    authors: Dice JF,Goldberg AL

    更新日期:1975-10-01 00:00:00

  • Primary structures of bovine liver low molecular weight kininogen precursors and their two mRNAs.

    abstract::By using a mixture of synthetic oligodeoxyribonucleotides as a probe, cloned cDNA sequences specific for low molecular weight (LMW) kininogen have been isolated from a cDNA library of bovine liver mRNA sequences. Nucleotide sequence analyses of cloned cDNA inserts have revealed that bovine liver LMW kininogens are enc...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.80.1.90

    authors: Nawa H,Kitamura N,Hirose T,Asai M,Inayama S,Nakanishi S

    更新日期:1983-01-01 00:00:00

  • Regulation of adenylate cyclase activity mediated by muscarinic acetylcholine receptors.

    abstract::Carbachol, an activator of muscarinic acetylcholine receptors of NG108-15 hybrid cells, inhibits adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] rapidly and reversibly and slowly evokes a 200-300% increase in adenylate cyclase activity over a period of 24-30 hr. Both the inhibition of adenylate cyc...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.75.4.1788

    authors: Nathanson NM,Klein WL,Nirenberg M

    更新日期:1978-04-01 00:00:00

  • The degree of extra-pair paternity increases with genetic variability.

    abstract::The amount of extra-pair paternity in socially monogamous bird species varies from 0% to 76% extra-pair offspring. The causes of this remarkable interspecific variation are largely unknown, although intraspecific analyses suggest that females seek extra-pair matings to improve the genetic quality of their offspring. I...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.16.9390

    authors: Petrie M,Doums C,Moller AP

    更新日期:1998-08-04 00:00:00

  • Nucleotide sequence of the 26S mRNA of Sindbis virus and deduced sequence of the encoded virus structural proteins.

    abstract::The nucleotide sequence of intracellular 26S mRNA of Sindbis virus has been determined by direct sequence analysis of the cDNA made to this RNA with reverse transcriptase. From this, the amino acid sequences of the encoded virus structural proteins, which include a basic capsid protein and two integral membrane glycop...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.78.4.2062

    authors: Rice CM,Strauss JH

    更新日期:1981-04-01 00:00:00

  • Polymorphism of HLA-DR beta chains in DR4, -7, and -9 haplotypes: implications for the mechanisms of allelic variation.

    abstract::We have isolated and sequenced cDNA clones corresponding to the DR beta 1 and DR beta 2 loci from two homozygous B-cell lines typed as DR7 (Burkhart) and DR9 (ISK). These nucleotide sequences were compared to beta 1 and beta 2 chains of other DR haplotypes. The first-domain sequences of beta 2 chains are identical in ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.23.9149

    authors: Gregersen PK,Moriuchi T,Karr RW,Obata F,Moriuchi J,Maccari J,Goldberg D,Winchester RJ,Silver J

    更新日期:1986-12-01 00:00:00

  • Glucose and glucosamine regulate growth factor gene expression in vascular smooth muscle cells.

    abstract::We have investigated the regulation of the expression of two growth factors found in vascular smooth muscle, transforming growth factor alpha (TGF alpha) and basic fibroblast growth factor (bFGF). Cells cultured in medium containing 30 mM glucose exhibited a 2-fold increase in TGF alpha mRNA and a 3-fold increase in b...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.17.8150

    authors: McClain DA,Paterson AJ,Roos MD,Wei X,Kudlow JE

    更新日期:1992-09-01 00:00:00

  • A muscle-type tropomyosin in human fibroblasts: evidence for expression by an alternative RNA splicing mechanism.

    abstract::We have isolated a cDNA clone from a human fibroblast cDNA library that contains the entire protein-coding region of a 1.1-kilobase mRNA. This mRNA encodes a 284-amino acid tropomyosin, the primary structure of which most closely resembles smooth muscle tropomyosin. Thus, the expression of both 284-amino acid muscle-t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.82.23.7835

    authors: MacLeod AR,Houlker C,Reinach FC,Smillie LB,Talbot K,Modi G,Walsh FS

    更新日期:1985-12-01 00:00:00

  • Different functional boundaries for the major antigenic region of two cytochromes c.

    abstract::The antigenic sites of horse and rat cytochromes c in the major antigenic region were compared using a panel of variant cytochromes c and a large number of BALB/c mouse monoclonal antibodies (mAbs) in competitive ELISAs. The major antigenic region of cytochrome c is located on the surface opposite of that containing t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.88.10.4428

    authors: Jemmerson R,Johnson JG

    更新日期:1991-05-15 00:00:00

  • In vitro characterization of DNA gyrase inhibition by microcin B17 analogs with altered bisheterocyclic sites.

    abstract::Microcin B17 (MccB17) is a 3.1-kDa Escherichia coli antibiotic that contains thiazole and oxazole heterocycles in a peptide backbone. MccB17 inhibits its cellular target, DNA gyrase, by trapping the enzyme in a complex that is covalently bound to double-strand cleaved DNA, in a manner similar to the well-known quinolo...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.141225698

    authors: Zamble DB,Miller DA,Heddle JG,Maxwell A,Walsh CT,Hollfelder F

    更新日期:2001-07-03 00:00:00

  • Comparative mapping of Andropogoneae: Saccharum L. (sugarcane) and its relation to sorghum and maize.

    abstract::Comparative genetic maps of Papuan Saccharum officinarum L. (2n = 80) and S. robustum (2n = 80) were constructed by using single-dose DNA markers (SDMs). SDM-framework maps of S. officinarum and S. robustum were compared with genetic maps of sorghum and maize by way of anchor restriction fragment length polymorphism p...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.26.14261

    authors: Guimarães CT,Sills GR,Sobral BW

    更新日期:1997-12-23 00:00:00

  • Allosteric regulation of γ-secretase activity by a phenylimidazole-type γ-secretase modulator.

    abstract::γ-Secretase is an intramembrane-cleaving protease responsible for the generation of amyloid-β (Aβ) peptides. Recently, a series of compounds called γ-secretase modulators (GSMs) has been shown to decrease the levels of long toxic Aβ species (i.e., Aβ42), with a concomitant elevation of the production of shorter Aβ spe...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1402171111

    authors: Takeo K,Tanimura S,Shinoda T,Osawa S,Zahariev IK,Takegami N,Ishizuka-Katsura Y,Shinya N,Takagi-Niidome S,Tominaga A,Ohsawa N,Kimura-Someya T,Shirouzu M,Yokoshima S,Yokoyama S,Fukuyama T,Tomita T,Iwatsubo T

    更新日期:2014-07-22 00:00:00

  • Mild mitochondrial uncoupling impacts cellular aging in human muscles in vivo.

    abstract::Faster aging is predicted in more active tissues and animals because of greater reactive oxygen species generation. Yet age-related cell loss is greater in less active cell types, such as type II muscle fibers. Mitochondrial uncoupling has been proposed as a mechanism that reduces reactive oxygen species production an...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0610131104

    authors: Amara CE,Shankland EG,Jubrias SA,Marcinek DJ,Kushmerick MJ,Conley KE

    更新日期:2007-01-16 00:00:00

  • Competition and hybridization drive interspecific territoriality in birds.

    abstract::Costly interactions between species that arise as a by-product of ancestral similarities in communication signals are expected to persist only under specific evolutionary circumstances. Territorial aggression between species, for instance, is widely assumed to persist only when extrinsic barriers prevent niche diverge...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1921380117

    authors: Drury JP,Cowen MC,Grether GF

    更新日期:2020-06-09 00:00:00

  • Increasing disparities between resource inputs and outcomes, as measured by certain health deliverables, in biomedical research.

    abstract::Society makes substantial investments in biomedical research, searching for ways to better human health. The product of this research is principally information published in scientific journals. Continued investment in science relies on society's confidence in the accuracy, honesty, and utility of research results. A ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1504955112

    authors: Bowen A,Casadevall A

    更新日期:2015-09-08 00:00:00

  • Identification of the 5' end of Rous sarcoma virus RNA.

    abstract::The 5'-terminal triphosphate of the 35S RNA isolated from Rous sarcoma virus is blocked by 7-methylguanosine in 5' linkage with the penultimate nucleoside which is methylated in the 2'-O-ribose position, a type of endgroup found in all animal mRNAs investigated during the past year. The specific nuclease-resistant ter...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.9.3347

    authors: Keith J,Fraenkel-Conrat H

    更新日期:1975-09-01 00:00:00

  • Acetyl-CoA carboxylase from Escherichia coli: gene organization and nucleotide sequence of the biotin carboxylase subunit.

    abstract::Biotin carboxylase [biotin-carboxyl-carrier-protein:carbon-dioxide ligase (ADP-forming), EC 6.3.4.14] is the enzyme mediating the first step of the acetyl-CoA carboxylase [acetyl-CoA:carbon-dioxide ligase (ADP-forming), EC 6.4.1.2] reaction. We screened an Escherichia coli DNA library and a DNA fragment carrying the b...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.88.21.9730

    authors: Kondo H,Shiratsuchi K,Yoshimoto T,Masuda T,Kitazono A,Tsuru D,Anai M,Sekiguchi M,Tanabe T

    更新日期:1991-11-01 00:00:00

  • Characterization of cytopathic factors through genome-wide analysis of the Zika viral proteins in fission yeast.

    abstract::The Zika virus (ZIKV) causes microcephaly and the Guillain-Barré syndrome. Little is known about how ZIKV causes these conditions or which ZIKV viral protein(s) is responsible for the associated ZIKV-induced cytopathic effects, including cell hypertrophy, growth restriction, cell-cycle dysregulation, and cell death. W...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1619735114

    authors: Li G,Poulsen M,Fenyvuesvolgyi C,Yashiroda Y,Yoshida M,Simard JM,Gallo RC,Zhao RY

    更新日期:2017-01-17 00:00:00

  • Evaluating a groundwater supply contamination incident attributed to Marcellus Shale gas development.

    abstract::High-volume hydraulic fracturing (HVHF) has revolutionized the oil and gas industry worldwide but has been accompanied by highly controversial incidents of reported water contamination. For example, groundwater contamination by stray natural gas and spillage of brine and other gas drilling-related fluids is known to o...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1420279112

    authors: Llewellyn GT,Dorman F,Westland JL,Yoxtheimer D,Grieve P,Sowers T,Humston-Fulmer E,Brantley SL

    更新日期:2015-05-19 00:00:00

  • Intrinsic evolutionary constraints on protease structure, enzyme acylation, and the identity of the catalytic triad.

    abstract::The study of proteolysis lies at the heart of our understanding of biocatalysis, enzyme evolution, and drug development. To understand the degree of natural variation in protease active sites, we systematically evaluated simple active site features from all serine, cysteine and threonine proteases of independent linea...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1221050110

    authors: Buller AR,Townsend CA

    更新日期:2013-02-19 00:00:00

  • Multiple components of blood group A and B antigens in human erythrocyte membranes and their difference between A1 and A2 status.

    abstract::Human type O erythrocyte membranes were converted to type A1 by purified human A1-enzyme, to type A2 by purified human A2-enzyme, and to type B by purified human B-enzyme in the presence of radioactive sugar donors (i.e., UDP-N-acetylgalactosamine for A-enzyme and UDP-galactose for B-enzyme, respectively). Type A2 ery...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.77.5.2951

    authors: Fujii H,Yoshida A

    更新日期:1980-05-01 00:00:00

  • 5-methylcytosine is localized in nucleosomes that contain histone H1.

    abstract::We have developed a procedure for purifying highly specific polyclonal antibodies against 5-methylcytosine. These antibodies were used to probe the distribution of 5-methylcytosine among fractionated nucleosomes of mouse cell chromatin. Our results demonstrate that at least 80% of the 5-methylcytosine is localized in ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.80.18.5490

    authors: Ball DJ,Gross DS,Garrard WT

    更新日期:1983-09-01 00:00:00

  • Role of an RNA cleavage/poly(A) addition site in the production of membrane-bound and secreted IgM mRNA.

    abstract::The switch from membrane-bound to secreted IgM is accomplished by producing alternative forms of mRNA from a single mu heavy-chain gene. This process might be controlled at any of three steps--transcription termination, RNA splicing, or RNA cleavage/poly(A) addition. To distinguish between these possibilities, we have...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.82.24.8658

    authors: Danner D,Leder P

    更新日期:1985-12-01 00:00:00

  • Complete loss of the tumor suppressor MAD2 causes premature cyclin B degradation and mitotic failure in human somatic cells.

    abstract::MAD2 inhibits the anaphase-promoting complex when chromosomes are unattached to the mitotic spindle. It acts as a tumor suppressor gene because MAD2+/-cells enter anaphase early and display chromosome instability, leading to the formation of lung tumors in mice. Complete MAD2 inactivation has not been identified in hu...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0306069101

    authors: Michel L,Diaz-Rodriguez E,Narayan G,Hernando E,Murty VV,Benezra R

    更新日期:2004-03-30 00:00:00

  • Anti-mosquito midgut antibodies block development of Plasmodium falciparum and Plasmodium vivax in multiple species of Anopheles mosquitoes and reduce vector fecundity and survivorship.

    abstract::The mosquito midgut plays a central role in the sporogonic development of malaria parasites. We have found that polyclonal sera, produced against mosquito midguts, blocked the passage of Plasmodium falciparum ookinetes across the midgut, leading to a significant reduction of infections in mosquitoes. Anti-midgut mAbs ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.091447398

    authors: Lal AA,Patterson PS,Sacci JB,Vaughan JA,Paul C,Collins WE,Wirtz RA,Azad AF

    更新日期:2001-04-24 00:00:00

  • Rapid degradation of unassembled ribulose 1,5-bisphosphate carboxylase small subunits in chloroplasts.

    abstract::We have detected a proteolytic mechanism in chloroplasts that selectively and rapidly degrades the imported small subunit of ribulose 1,5-bisphosphate carboxylase when pools of the chloroplast-synthesized large subunit are depleted. This degradation system is constitutively present and appears to be responsible for pr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.80.9.2632

    authors: Schmidt GW,Mishkind ML

    更新日期:1983-05-01 00:00:00

  • Facilitating and nonfacilitating synapses on pyramidal cells: a correlation between physiology and morphology.

    abstract::Pyramidal cells in piriform cortex receive excitatory inputs from two different sources that are segregated onto adjacent segments of their apical dendrites. The present studies show that excitatory postsynaptic potentials (EPSPs) evoked by primary olfactory tract afferents that terminate on distal apical segments dis...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.4.1115

    authors: Bower JM,Haberly LB

    更新日期:1986-02-01 00:00:00