The acidic tail of HMGB1 regulates its secondary structure and conformational flexibility: A circular dichroism and molecular dynamics simulation study

Computational and Structural Biotechnology Journal
Wresti L AnggayastiRicardo L Mancera

Abstract

High mobility group box 1 (HMGB1) is a damage-associated molecular pattern (DAMP) molecule that triggers the progression of several pro-inflammatory diseases such as diabetes, Alzheimer's disease and cancer, by inducing signals upon interaction with the receptors such as the receptor for advanced glycation end-products (RAGE) and toll-like receptors (TLRs). The acidic C-terminal tail of HMGB1 is an intrinsically disordered region of the protein which is known to determine the interaction of HMGB1 to DNA and histones. This study characterizes its structural properties using a combination of circular dichroism (CD) and molecular dynamics (MD) simulations. The full-length and tail-less forms of HMGB1 were compared to rationalise the role of the acidic tail in maintaining the stability of the entire structure of HMGB1 in atomistic detail. Consistent with experimental data, the acidic tail was predicted to adopt an extended conformation that allows it to make a range of hydrogen-bonding and electrostatic interactions with the box-like domains that stabilize the overall structure of HMGB1. Absence of the acidic tail was predicted to increase structural fluctuations of all amino acids, leading to changes in secondary structure from α-...Continue Reading

References

Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
May 22, 2007·The Journal of Nutrition·Dennis A Dougherty
Nov 9, 2007·Journal of Molecular Biology·Matthew WatsonJean O Thomas
Jun 11, 2008·Methods in Molecular Biology·Narayanan EswarAndrej Sali
Mar 13, 2009·The Protein Journal·Sasa N MalkovSnezana D Zarić
Nov 17, 2009·Biochimica Et Biophysica Acta·Heikki Rauvala, Ari Rouhiainen
Jun 16, 2010·PLoS Computational Biology·Semen O YesylevskyySiewert J Marrink
Oct 14, 2014·Israel Journal of Chemistry·N P SchaferP G Wolynes
Dec 23, 2014·Nature Reviews. Molecular Cell Biology·Peter E Wright, H Jane Dyson
Sep 26, 2015·PloS One·Michal ŠtrosŠárka Pospíšilová
Mar 1, 2008·Journal of Chemical Theory and Computation·Berk HessErik Lindahl
May 1, 2008·Journal of Chemical Theory and Computation·Luca MonticelliSiewert-Jan Marrink
Feb 13, 2016·Analytical Biochemistry·Wresti L AnggayastiErik Helmerhorst
Jun 23, 2016·Chemical Reviews·Sebastian KmiecikAndrzej Kolinski
Aug 26, 2016·Journal of Molecular Biology·Rebecca H BlairJennifer F Kugel
Sep 24, 2016·Cell·Agnes Toth-PetroczyDebora S Marks
Oct 30, 2016·Proceedings of the National Academy of Sciences of the United States of America·Weihua ZhengPeter G Wolynes
Oct 19, 2005·Biophysics·Kenichiro Imai, Shigeki Mitaku
Dec 22, 2017·Journal of Medicinal Chemistry·Sonya VanPatten, Yousef Al-Abed
Aug 29, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sandra J MooreRicardo L Mancera
Sep 22, 2018·Journal of Biomolecular Structure & Dynamics·Shan SunYousef Al-Abed

❮ Previous
Next ❯

Citations

Oct 30, 2020·Cells·Nina D AnfinogenovaDmitriy N Atochin
Jun 24, 2021·Human Genetics·Jonas ElsnerMalte Spielmann

❮ Previous
Next ❯

Methods Mentioned

BETA
NMR
circular dichroism

Software Mentioned

CONTIN
GROMACS
DichroWeb
MODELLER
DSSP
MARTINI

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.

Related Papers

Nihon rinsho. Japanese journal of clinical medicine
Ikuro Maruyama, Shingo Yamada
Nihon rinsho. Japanese journal of clinical medicine
Ikuro Maruyama
Journal of Cellular Physiology
Jiaming XueHaining Yang
© 2022 Meta ULC. All rights reserved