Translation and folding of single proteins in real time

Proceedings of the National Academy of Sciences of the United States of America
Florian WruckMartin Hegner

Abstract

Protein biosynthesis is inherently coupled to cotranslational protein folding. Folding of the nascent chain already occurs during synthesis and is mediated by spatial constraints imposed by the ribosomal exit tunnel as well as self-interactions. The polypeptide's vectorial emergence from the ribosomal tunnel establishes the possible folding pathways leading to its native tertiary structure. How cotranslational protein folding and the rate of synthesis are linked to a protein's amino acid sequence is still not well defined. Here, we follow synthesis by individual ribosomes using dual-trap optical tweezers and observe simultaneous folding of the nascent polypeptide chain in real time. We show that observed stalling during translation correlates with slowed peptide bond formation at successive proline sequence positions and electrostatic interactions between positively charged amino acids and the ribosomal tunnel. We also determine possible cotranslational folding sites initiated by hydrophobic collapse for an unstructured and two globular proteins while directly measuring initial cotranslational folding forces. Our study elucidates the intricate relationship among a protein's amino acid sequence, its cotranslational nascent-chain...Continue Reading

References

Sep 1, 1999·Proceedings of the National Academy of Sciences of the United States of America·M HegnerC Bustamante
Apr 28, 2001·Science·J LiphardtC Bustamante
Mar 4, 2003·Proceedings of the National Academy of Sciences of the United States of America·Elizabeth RhoadesGilad Haran
Oct 8, 2003·Proceedings of the National Academy of Sciences of the United States of America·Mourad SadqiVictor Muñoz
Dec 6, 2003·Science·Charles L AsburySteven M Block
Jan 27, 2005·Proceedings of the National Academy of Sciences of the United States of America·Takatsugu KobayashiShigeyuki Yokoyama
Nov 15, 2005·Nature·Elio A AbbondanzieriSteven M Block
Jun 6, 2006·Proceedings of the National Academy of Sciences of the United States of America·Jeffrey R MoffittCarlos Bustamante
Jun 21, 2006·Journal of Molecular Biology·N R VossP B Moore
Aug 16, 2006·Proceedings of the National Academy of Sciences of the United States of America·Hendrik DietzMatthias Rief
Mar 3, 2007·Annual Review of Biophysics and Biomolecular Structure·William J GreenleafSteven M Block
Apr 10, 2007·Biophysical Journal·Lisa J LapidusOlgica Bakajin
Oct 18, 2007·Proceedings of the National Academy of Sciences of the United States of America·Shang-Te Danny HsuJohn Christodoulou
Jan 29, 2008·Current Opinion in Structural Biology·Benjamin Schuler, William A Eaton
Feb 29, 2008·PLoS Biology·Wilfried GrangeMartin Hegner
Mar 11, 2008·Nature·Jin-Der WenIgnacio Tinoco
Jan 29, 2009·Angewandte Chemie·Alexandros KatranidisJörg Fitter
Jan 29, 2009·ACS Chemical Biology·Shinichiro ShojiKurt Fredrick
Feb 10, 2009·Nature Structural & Molecular Biology·Gong ZhangZoya Ignatova
Feb 20, 2009·PLoS Biology·Marco D MukraschMarkus Zweckstetter
Apr 14, 2009·Trends in Biochemical Sciences·Achillefs N Kapanidis, Terence Strick
Mar 10, 2010·Current Pharmaceutical Biotechnology·Hiroyuki OhashiTakuya Ueda
Jan 6, 2011·Journal of the American Chemical Society·Edward P O'BrienChristopher M Dobson
Dec 24, 2011·Science·Christian M KaiserCarlos Bustamante
Oct 23, 2012·Archives of Biochemistry and Biophysics·Jayant B Udgaonkar
Apr 5, 2013·PLoS Biology·Catherine A Charneski, Laurence D Hurst
Sep 5, 2013·Proceedings of the National Academy of Sciences of the United States of America·Lauri PeilDaniel N Wilson
Nov 6, 2013·Proceedings of the National Academy of Sciences of the United States of America·Benjamin T WaltersS Walter Englander
Apr 12, 2014·Current Opinion in Structural Biology·Felix GlogeBernd Bukau
Jun 6, 2014·PLoS Genetics·Fabienne F V ChevanceKelly T Hughes
Jun 12, 2014·Nature·Jin ChenJoseph D Puglisi
Oct 14, 2014·Journal of Molecular Biology·Jianli Lu, Carol Deutsch
Sep 1, 2015·Cell Reports·Ola B NilssonGunnar von Heijne
Nov 28, 2015·Science·Wolf HoltkampMarina V Rodnina
Feb 26, 2016·Journal of Molecular Biology·Ola B NilssonGunnar von Heijne
Mar 1, 2016·Beilstein Journal of Nanotechnology·Vivek S JadhavMartin Hegner

❮ Previous
Next ❯

Citations

Feb 24, 2018·Chemical Society Reviews·Jörg SchönfelderRaul Perez-Jimenez
Sep 10, 2019·Physical Chemistry Chemical Physics : PCCP·Maziar HeidariAlireza Mashaghi
Sep 26, 2019·Current Protein & Peptide Science·Dániel HorváthAndrás Perczel
Jan 29, 2020·Journal of Lipid Research·Lahoucine IzemRichard E Morton
Jun 22, 2019·Nature Communications·Lisa M AlexanderCarlos Bustamante
Jun 23, 2020·Annual Review of Biochemistry·Carlos BustamanteChristian M Kaiser
Sep 26, 2020·International Journal of Molecular Sciences·Gesche K GerresheimMichael Niepmann
Jun 27, 2018·International Journal of Molecular Sciences·Alf MånssonDilson E Rassier
Jan 16, 2020·Biomolecules·Marija LiutkuteMarina V Rodnina
Apr 17, 2019·Nature Communications·Ivanka KamenovaLászló Tora
Nov 11, 2018·Proceedings of the National Academy of Sciences of the United States of America·Pengfei TianRobert B Best
Oct 11, 2020·Nature Communications·Xiuqi ChenChristian M Kaiser
Nov 18, 2019·Biochimica Et Biophysica Acta. General Subjects·Melissa C PiontekWouter H Roos
Jul 1, 2020·Ageing Research Reviews·Stephany FranciscoManuel A S Santos
Aug 29, 2020·Biophysical Journal·Victor ZhaoEugene I Shakhnovich
Mar 2, 2021·Annual Review of Biophysics·Souradeep BanerjeeShubhasis Haldar
May 7, 2021·Communications Biology·Florian WruckAlexandros Katranidis
May 15, 2021·Journal of Molecular Biology·Hena SandhuGunnar von Heijne
Jan 17, 2019·Analytical Chemistry·Alexandros Katranidis, Jörg Fitter
Sep 11, 2018·The Journal of Physical Chemistry. B·Pawel Dabrowski-TumanskiJoanna I Sulkowska
Nov 24, 2021·Biophysical Journal·John M McBride, Tsvi Tlusty

❮ Previous
Next ❯

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.