Molecular basis for diversification of yeast prion strain conformation

Proceedings of the National Academy of Sciences of the United States of America
Yumiko OhhashiMotomasa Tanaka

Abstract

Self-propagating β-sheet-rich fibrillar protein aggregates, amyloid fibers, are often associated with cellular dysfunction and disease. Distinct amyloid conformations dictate different physiological consequences, such as cellular toxicity. However, the origin of the diversity of amyloid conformation remains unknown. Here, we suggest that altered conformational equilibrium in natively disordered monomeric proteins leads to the adaptation of alternate amyloid conformations that have different phenotypic effects. We performed a comprehensive high-resolution structural analysis of Sup35NM, an N-terminal fragment of the Sup35 yeast prion protein, and found that monomeric Sup35NM harbored latent local compact structures despite its overall disordered conformation. When the hidden local microstructures were relaxed by genetic mutations or solvent conditions, Sup35NM adopted a strikingly different amyloid conformation, which redirected chaperone-mediated fiber fragmentation and modulated prion strain phenotypes. Thus, dynamic conformational fluctuations in natively disordered monomeric proteins represent a posttranslational mechanism for diversification of aggregate structures and cellular phenotypes.

References

Mar 11, 2004·Molecular Microbiology·Michael E Bradley, Susan W Liebman
Mar 19, 2004·Nature·Chih-Yen King, Ruben Diaz-Avalos
Aug 3, 2004·Science·Giuseppe LegnameStanley B Prusiner
Oct 7, 2004·The Journal of Biological Chemistry·Sviatoslav Bagriantsev, Susan W Liebman
Jun 10, 2005·Nature·Rajaraman Krishnan, Susan L Lindquist
Nov 25, 2005·Current Genetics·Andrey S BorchseniusYury O Chernoff
Jul 1, 2006·Nature·Motomasa TanakaJonathan S Weissman
Dec 16, 2006·Proceedings of the National Academy of Sciences of the United States of America·Frank ShewmakerRobert Tycko
Feb 15, 2007·Proceedings of the National Academy of Sciences of the United States of America·Samrat MukhopadhyayAshok A Deniz
Sep 4, 2007·Nature·Brandon H ToyamaJonathan S Weissman
Nov 10, 2007·Science·John Collinge, Anthony R Clarke
Jan 19, 2010·Nature Chemical Biology·Yumiko OhhashiMotomasa Tanaka
Nov 18, 2010·Nature Reviews. Molecular Cell Biology·Mick F Tuite, Tricia R Serio
Nov 15, 2011·The Journal of Biological Chemistry·Christopher W Helsen, John R Glover
Mar 20, 2012·Cell·David Eisenberg, Mathias Jucker
Aug 8, 2012·The Journal of Cell Biology·Juliane WinklerAxel Mogk
Aug 11, 2012·Genetics·Susan W Liebman, Yury O Chernoff
Jun 12, 2013·Molecular Cell·Ricardo MarchanteMick F Tuite
Aug 31, 2013·The Journal of Biological Chemistry·Jonathan RubinAndreas S Bommarius
May 24, 2014·Nature Reviews. Molecular Cell Biology·Tuomas P J KnowlesChristopher M Dobson
May 17, 2015·Nature Chemical Biology·Motomasa Tanaka, Yusuke Komi

❮ Previous
Next ❯

Citations

May 31, 2018·FEMS Yeast Research·Rupam GhoshKendra K Frederick
Dec 27, 2019·Prion·Vitaly V KushnirovAlexander I Alexandrov
Dec 12, 2018·ELife·Apurwa M SharmaMarc I Diamond
May 31, 2019·International Journal of Molecular Sciences·Alexander A DergalevVitaly V Kushnirov
Jun 12, 2019·Current Genetics·Yu-Wen Huang, Chih-Yen King
Apr 15, 2020·Nature Chemical Biology·Toshinobu ShidaMotomasa Tanaka
Jul 9, 2020·International Journal of Molecular Sciences·Reed B WicknerMadaleine Niznikiewicz
Feb 21, 2019·Proceedings of the National Academy of Sciences of the United States of America·Eleanor FlemingAnn Hochschild
Nov 16, 2020·Molecular Microbiology·Yu-Wen HuangChih-Yen King
Jan 31, 2021·International Journal of Molecular Sciences·Anastasia Fomicheva, Eric D Ross
Apr 9, 2021·Acta Neuropathologica·Jaime Vaquer-AliceaLukasz A Joachimiak
May 1, 2021·International Journal of Molecular Sciences·Eri ChataniYuji Goto
Jun 18, 2021·Chemical Reviews·Dieter WillboldHenrike Heise
Jul 2, 2021·Scientific Reports·Zhiqiang HouLukasz A Joachimiak
Jul 29, 2021·Current Genetics·Reed B WicknerMadaleine Niznikiewicz

❮ 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.