Solution Structure of the Catalytic Domain of the Mitochondrial Protein ICT1 That Is Essential for Cell Vitality

Handa, Yoshihiro; Hikawa, Yusuke; Tochio, N.; Kogure, Hiroyuki; Inoue, Makoto; Koshiba, S.; Güntert, Peter; Inoue, Yusuke; Kigawa, T.; Yokoyama, Shigeyuki; Nameki, Nobukazu

doi:10.1016/j.jmb.2010.09.033

Cited by 48 publications

(78 citation statements)

References 39 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For ArfB/YaeJ and ICT1, the N-terminal globular domain is shown in blue. ( B ) Comparison of 3D-structures of Thermus thermophilus RF2 [14] (PDB code 2WH1), E. coli ArfB/YaeJ [5] (PDB code 4DH9), and mouse ICT1 [26] (PDB code 1J26). Each domain of RF2, ArfB and ICT1 is shown in the same colors as in (A).…”

Section: Resultsmentioning

confidence: 99%

Ribosome Rescue and Translation Termination at Non-Standard Stop Codons by ICT1 in Mammalian Mitochondria

et al. 2014

View full text Add to dashboard Cite

Release factors (RFs) govern the termination phase of protein synthesis. Human mitochondria harbor four different members of the class 1 RF family: RF1Lmt/mtRF1a, RF1mt, C12orf65 and ICT1. The homolog of the essential ICT1 factor is widely distributed in bacteria and organelles and has the peculiar feature in human mitochondria to be part of the ribosome as a ribosomal protein of the large subunit. The factor has been suggested to rescue stalled ribosomes in a codon-independent manner. The mechanism of action of this factor was obscure and is addressed here. Using a homologous mitochondria system of purified components, we demonstrate that the integrated ICT1 has no rescue activity. Rather, purified ICT1 binds stoichiometrically to mitochondrial ribosomes in addition to the integrated copy and functions as a general rescue factor, i.e. it releases the polypeptide from the peptidyl tRNA from ribosomes stalled at the end or in the middle of an mRNA or even from non-programmed ribosomes. The data suggest that the unusual termination at a sense codon (AGA/G) of the oxidative-phosphorylation enzymes CO1 and ND6 is also performed by ICT1 challenging a previous model, according to which RF1Lmt/mtRF1a is responsible for the translation termination at non-standard stop codons. We also demonstrate by mutational analyses that the unique insertion sequence present in the N-terminal domain of ICT1 is essential for peptide release rather than for ribosome binding. The function of RF1mt, another member of the class1 RFs in mammalian mitochondria, was also examined and is discussed.

show abstract

Section: Resultsmentioning

confidence: 99%

Ribosome Rescue and Translation Termination at Non-Standard Stop Codons by ICT1 in Mammalian Mitochondria

et al. 2014

View full text Add to dashboard Cite

show abstract

“…The ICT1 gene was recently reported to be a component of the human mitoribosome essential for cell viability. 41 HN1 encodes hemopoietic- and neurological-expressed sequence-1 involved in neuronal regeneration. 42 SLC16A5 gene is a mono-carboxylate transporter similar to MCT1, which had been involved in mediating axon damage.…”

Section: Discussionmentioning

confidence: 99%

ATP5H/KCTD2 locus is associated with Alzheimer's disease risk

et al. 2013

View full text Add to dashboard Cite

To identify loci associated with Alzheimer disease, we conducted a three-stage analysis using existing genome-wide association studies (GWAS) and genotyping in a new sample. In Stage I, all suggestive single-nucleotide polymorphisms (at P<0.001) in a previously reported GWAS of seven independent studies (8082 Alzheimer's disease (AD) cases; 12 040 controls) were selected, and in Stage II these were examined in an in silico analysis within the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium GWAS (1367 cases and 12904 controls). Six novel signals reaching P<5 × 10−6 were genotyped in an independent Stage III sample (the Fundació ACE data set) of 2200 sporadic AD patients and 2301 controls. We identified a novel association with AD in the adenosine triphosphate (ATP) synthase, H+ transporting, mitochondrial F0 (ATP5H)/Potassium channel tetramerization domain-containing protein 2 (KCTD2) locus, which reached genome-wide significance in the combined discovery and genotyping sample (rs11870474, odds ratio (OR)=1.58, P=2.6 × 10−7 in discovery and OR=1.43, P=0.004 in Fundació ACE data set; combined OR=1.53, P=4.7 × 10−9). This ATP5H/KCTD2 locus has an important function in mitochondrial energy production and neuronal hyperpolarization during cellular stress conditions, such as hypoxia or glucose deprivation.

show abstract

“…The alignment was further compared with the solution structure of the Mus musculus ICT1 (ref. 34) to get the correct secondary structure alignment. The helix close to the C-terminal end (missing in ref.…”

Section: Methodsmentioning

confidence: 99%

“…The helix close to the C-terminal end (missing in ref. 34) was modelled as predicted by PSIPRED 28 (Fig. 7).…”

Section: Methodsmentioning

confidence: 99%

Codon-reading specificities of mitochondrial release factors and translation termination at non-standard stop codons

2013

View full text Add to dashboard Cite

A key feature of mitochondrial translation is the reduced number of transfer RNAs and reassignment of codons. For human mitochondria, a major unresolved problem is how the set of stop codons are decoded by the release factors mtRF1a and mtRF1. Here we present threedimensional structural models of human mtRF1a and mtRF1 based on their homology to bacterial RF1 in the codon recognition domain, and the strong conservation between mitochondrial and bacterial ribosomal RNA in the decoding region. Sequence changes in the less homologous mtRF1 appear to be correlated with specific features of the mitochondrial rRNA. Extensive computer simulations of the complexes with the ribosomal decoding site show that both mitochondrial factors have similar specificities and that neither reads the putative vertebrate stop codons AGA and AGG. Instead, we present a structural model for a mechanism by which the ICT1 protein causes termination by sensing the presence of these codons in the A-site of stalled ribosomes.

show abstract

Solution Structure of the Catalytic Domain of the Mitochondrial Protein ICT1 That Is Essential for Cell Vitality

Cited by 48 publications

References 39 publications

Ribosome Rescue and Translation Termination at Non-Standard Stop Codons by ICT1 in Mammalian Mitochondria

Ribosome Rescue and Translation Termination at Non-Standard Stop Codons by ICT1 in Mammalian Mitochondria

ATP5H/KCTD2 locus is associated with Alzheimer's disease risk

Codon-reading specificities of mitochondrial release factors and translation termination at non-standard stop codons

Contact Info

Product

Resources

About