The transition state structure for binding between TAZ1 of CBP and the disordered Hif-1α CAD

Scientific Reports
Ida LindströmJakob Dogan

Abstract

Intrinsically disordered proteins (IDPs) are common in eukaryotes. However, relatively few experimental studies have addressed the nature of the rate-limiting transition state for the coupled binding and folding reactions involving IDPs. By using site-directed mutagenesis in combination with kinetics measurements we have here characterized the transition state for binding between the globular TAZ1 domain of CREB binding protein and the intrinsically disordered C-terminal activation domain of Hif-1α (Hif-1α CAD). A total of 17 Hif-1α CAD point-mutations were generated and a Φ-value binding analysis was carried out. We found that native hydrophobic binding interactions are not formed at the transition state. We also investigated the effect the biologically important Hif-1α CAD Asn-803 hydroxylation has on the binding kinetics, and found that the whole destabilization effect due the hydroxylation is within the dissociation rate constant. Thus, the rate-limiting transition state is "disordered-like", with native hydrophobic binding contacts being formed cooperatively after the rate-limiting barrier, which is clearly shown by linear free energy relationships. The same behavior was observed in a previously characterized TAZ1/IDP inte...Continue Reading

References

Jan 20, 1995·Science·T Clackson, J A Wells
May 31, 2001·Journal of Molecular Graphics & Modelling·A K DunkerZ Obradovic
Aug 23, 2001·Trends in Molecular Medicine·G L Semenza
Feb 2, 2002·Science·David LandoMurray L Whitelaw
Apr 18, 2002·Proceedings of the National Academy of Sciences of the United States of America·Sonja A DamesPeter E Wright
Jan 12, 2005·Biochemistry·Roberto N De GuzmanPeter E Wright
Feb 5, 2005·Trends in Biochemical Sciences·Michael J PlevinMitsuhiko Ikura
May 18, 2005·Biophysical Chemistry·Francesco Malatesta
Apr 12, 2008·PLoS Computational Biology·Adrian Gustavo TurjanskiGerhard Hummer
Feb 7, 2009·Chemical Reviews·G SchreiberH-X Zhou
Feb 18, 2011·Proceedings of the National Academy of Sciences of the United States of America·Annett BachmannThomas Kiefhaber
Jul 7, 2011·Quarterly Reviews of Biophysics·H Jane Dyson
Jan 12, 2013·Cellular and Molecular Life Sciences : CMLS·Feng WangMitsuhiko Ikura
Aug 28, 2013·Proceedings of the National Academy of Sciences of the United States of America·Rajanish GiriStefano Gianni
Dec 10, 2013·Physical Chemistry Chemical Physics : PCCP·Jakob DoganPer Jemth
Apr 18, 2014·Chemical Reviews·Johnny HabchiVladimir N Uversky
Apr 30, 2014·Chemical Reviews·Robin van der LeeM Madan Babu
Jun 19, 2014·Cellular and Molecular Life Sciences : CMLS·Zhenling PengLukasz Kurgan
Oct 15, 2014·Proceedings of the National Academy of Sciences of the United States of America·Joseph M RogersJane Clarke
Dec 23, 2014·Nature Reviews. Molecular Cell Biology·Peter E Wright, H Jane Dyson

❮ Previous
Next ❯

Citations

Dec 6, 2018·The Journal of Biological Chemistry·Elin KarlssonCarlo Camilloni
Aug 24, 2019·Protein Science : a Publication of the Protein Society·Jing YangYongqi Huang
Apr 4, 2020·Physical Chemistry Chemical Physics : PCCP·Irene Ruiz-Ortiz, David De Sancho
Apr 8, 2020·The Journal of Biological Chemistry·Angelo TotoStefano Gianni
Jul 17, 2020·Frontiers in Molecular Biosciences·Joseph M Rogers
Mar 4, 2020·Proceedings of the National Academy of Sciences of the United States of America·Wen-Ting ChuJin Wang
Oct 18, 2020·The Journal of Biological Chemistry·Elin KarlssonPer Jemth
Jul 22, 2019·Archives of Biochemistry and Biophysics·Angelo TotoStefano Gianni
Nov 20, 2020·International Journal of Molecular Sciences·Monika Fuxreiter
Jan 18, 2021·The Journal of Biological Chemistry·Elin KarlssonPer Jemth
Mar 13, 2019·The Journal of Physical Chemistry. B·Ida NyqvistJakob Dogan
Jan 16, 2020·The Journal of Physical Chemistry Letters·Yanming Wang, Charles L Brooks Iii
Sep 11, 2021·Proceedings of the National Academy of Sciences of the United States of America·San HadžiJurij Lah

❮ Previous
Next ❯

Methods Mentioned

BETA
NMR
reversed phase chromatography

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.