Structural metamorphism and polymorphism in proteins on the brink of thermodynamic stability

Protein Science : a Publication of the Protein Society
Prakash KulkarniJohn Orban

Abstract

The classical view of the structure-function paradigm advanced by Anfinsen in the 1960s is that a protein's function is inextricably linked to its three-dimensional structure and is encrypted in its amino acid sequence. However, it is now known that a significant fraction of the proteome consists of intrinsically disordered proteins (IDPs). These proteins populate a polymorphic ensemble of conformations rather than a unique structure but are still capable of performing biological functions. At the boundary, between well-ordered and inherently disordered states are proteins that are on the brink of stability, either weakly stable ordered systems or disordered but on the verge of being stable. In such marginal states, even relatively minor changes can significantly alter the energy landscape, leading to large-scale conformational remodeling. Some proteins on the edge of stability are metamorphic, with the capacity to switch from one fold topology to another in response to an environmental trigger (e.g., pH, temperature/salt, redox). Many IDPs, on the other hand, are marginally unstable such that small perturbations (e.g., phosphorylation, ligands) tip the balance over to a range of ordered, partially ordered, or even more disorde...Continue Reading

References

Jan 1, 1992·Progress in Nucleic Acid Research and Molecular Biology·R Somerville
Jul 20, 1973·Science·C B Anfinsen
Jul 1, 1997·Nature Structural Biology·G D Rose
Jul 1, 1997·Nature Structural Biology·S DalalL Regan
Mar 7, 1998·Proteins·S M Yuan, N D Clarke
Aug 5, 1998·Proceedings of the National Academy of Sciences of the United States of America·H WuX Q Liu
Feb 13, 1999·Nature Genetics·R B IrbyT J Yeatman
Nov 5, 1999·Journal of Molecular Biology·P E Wright, H J Dyson
Jan 5, 2000·Proceedings of the National Academy of Sciences of the United States of America·R ZahnK Wüthrich
Dec 2, 2000·Nature Structural Biology·M H CordesR T Sauer
Apr 5, 2001·Journal of Molecular Biology·D EliezerG Browne
May 24, 2001·Proceedings of the National Academy of Sciences of the United States of America·P ZhouG Wagner
Sep 12, 2001·Journal of Structural Biology·N V Grishin
Apr 18, 2002·Proceedings of the National Academy of Sciences of the United States of America·Sonja A DamesPeter E Wright
Dec 12, 2002·Chemical Reviews·Peter G W Gettins
Dec 1, 1959·Journal of Cellular and Comparative Physiology·D E KOSHLAND
Sep 23, 2003·Protein Science : a Publication of the Protein Society·Ryan DayValerie Daggett
Mar 17, 2004·Nature Structural & Molecular Biology·Xuelian LuoHongtao Yu
Apr 6, 2004·Structure·Tracey NewloveMatthew H J Cordes
Dec 24, 2004·The Journal of Biological Chemistry·Tobias S UlmerRobert L Nussbaum
Mar 2, 2005·Nature Reviews. Molecular Cell Biology·H Jane Dyson, Peter E Wright
Jun 3, 2005·Protein Science : a Publication of the Protein Society·Noel D LazoDavid B Teplow
Nov 19, 2005·Proceedings of the National Academy of Sciences of the United States of America·Thorsten LührsRoland Riek
Aug 4, 2006·PLoS Computational Biology·Chad HaynesLilia M Iakoucheva
Jan 24, 2007·Current Biology : CB·Sebastian MeierSuat Ozbek
Jun 29, 2007·Proceedings of the National Academy of Sciences of the United States of America·Leonid MeyerguzRon Elber
Jul 5, 2007·Proceedings of the National Academy of Sciences of the United States of America·Patrick A AlexanderPhilip N Bryan
Jan 30, 2008·Proceedings of the National Academy of Sciences of the United States of America·Christian G RoesslerMatthew H J Cordes
Mar 28, 2008·Proceedings of the National Academy of Sciences of the United States of America·Robbyn L TuinstraBrian F Volkman

❮ Previous
Next ❯

Citations

Aug 28, 2019·Proceedings of the National Academy of Sciences of the United States of America·Rui YangVann Bennett
Aug 29, 2019·Chembiochem : a European Journal of Chemical Biology·Héctor Zamora-CarrerasM Angeles Jiménez
Nov 11, 2018·Biomolecules·Sharonda J LeBlancKeith R Weninger
Dec 15, 2019·Nature Communications·Luis A CamposVictor Muñoz
Oct 14, 2020·PLoS Computational Biology·Pengfei Tian, Robert B Best
Nov 12, 2020·Structure·Allen K Kim, Lauren L Porter
Sep 17, 2020·Biophysical Journal·Nanhao ChenLee-Ping Wang

❮ 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.

© 2022 Meta ULC. All rights reserved