Distinct pre-initiation steps in human mitochondrial translation.

Nature Communications
Anas KhawajaJoanna Rorbach

Abstract

Translation initiation in human mitochondria relies upon specialized mitoribosomes and initiation factors, mtIF2 and mtIF3, which have diverged from their bacterial counterparts. Here we report two distinct mitochondrial pre-initiation assembly steps involving those factors. Single-particle cryo-EM revealed that in the first step, interactions between mitochondria-specific protein mS37 and mtIF3 keep the small mitoribosomal subunit in a conformation favorable for a subsequent accommodation of mtIF2 in the second step. Combination with fluorescence cross-correlation spectroscopy analyses suggests that mtIF3 promotes complex assembly without mRNA or initiator tRNA binding, where exclusion is achieved by the N-terminal and C-terminal domains of mtIF3. Finally, the association of large mitoribosomal subunit is required for initiator tRNA and leaderless mRNA recruitment to form a stable initiation complex. These data reveal fundamental aspects of mammalian protein synthesis that are specific to mitochondria.

References

May 18, 1999·Journal of Molecular Biology·C SacerdotM Springer
Aug 23, 2001·Proceedings of the National Academy of Sciences of the United States of America·N A BakerJ A McCammon
Jun 25, 2004·Nucleic Acids Research·Isabella MollUdo Bläsi
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Mar 4, 2011·Proceedings of the National Academy of Sciences of the United States of America·Aymen S YassinRajendra K Agrawal
Sep 14, 2013·Proceedings of the National Academy of Sciences of the United States of America·Angelita SimonettiBruno P Klaholz
Apr 4, 2015·Science·Alexey AmuntsV Ramakrishnan
Nov 26, 2015·Journal of Structural Biology·Kai Zhang
Apr 25, 2017·Scientific Reports·Noémie KempfJörg Fitter
Jul 16, 2017·Protein Science : a Publication of the Protein Society·Thomas D GoddardThomas E Ferrin
Oct 23, 2018·Journal of Visualized Experiments : JoVE·Shintaro AibaraAlexey Amunts
Jan 7, 2020·Science Advances·Danielle L RudlerAleksandra Filipovska

❮ Previous
Next ❯

Citations

Aug 20, 2020·ELife·Shintaro AibaraAlexey Amunts
Aug 9, 2020·Frontiers in Genetics·M Isabel G Lopez SanchezJoanna Rorbach
Oct 20, 2020·Frontiers in Microbiology·Emmanuelle SchmittYves Mechulam
Nov 11, 2020·Proceedings of the National Academy of Sciences of the United States of America·Heddy SoufariYaser Hashem
Dec 15, 2020·FEBS Letters·Alberto FerrariAntoni Barrientos
Feb 18, 2021·Nature Reviews. Molecular Cell Biology·Eva Kummer, Nenad Ban
Feb 20, 2021·Science·Yuzuru ItohAlexey Amunts
May 1, 2021·International Journal of Molecular Sciences·Maria Isabel G Lopez SanchezJoanna Rorbach
May 1, 2021·Biochemical Society Transactions·Zhen LiaoAlexandre Smirnov
Jun 11, 2021·RNA Biology·Huixin LiangQiyi Zhao
Jul 29, 2021·Nature Communications·Jingdong ChengRoland Beckmann
Dec 21, 2021·RNA Biology·Franziska NadlerRicarda Richter-Dennerlein

❮ Previous
Next ❯

Methods Mentioned

BETA
GTPase
immunoprecipitation
fluorescence
cross-correlation spectroscopy
confocal microscopy
optical tweezers
FCS
gel filtration
electrophoresis
optical tweezer

Software Mentioned

BlueLake
PHENIX
UCSF Chimera
Gautomatch
ImageJ
EPU
Gctf
PyMOL
RELION
UCSF ChimeraX

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.