Structural insights into SETD3-mediated histidine methylation on β-actin

ELife
Qiong GuoChao Xu

Abstract

SETD3 is a member of the SET (Su(var)3-9, Enhancer of zeste, and Trithorax) domain protein superfamily and plays important roles in hypoxic pulmonary hypertension, muscle differentiation, and carcinogenesis. Previously, we identified SETD3 as the actin-specific methyltransferase that methylates the N3 of His73 on β-actin (Kwiatkowski et al., 2018). Here, we present two structures of S-adenosyl-L-homocysteine-bound SETD3 in complex with either an unmodified β-actin peptide or its His-methylated variant. Structural analyses, supported by biochemical experiments and enzyme activity assays, indicate that the recognition and methylation of β-actin by SETD3 are highly sequence specific, and that both SETD3 and β-actin adopt pronounced conformational changes upon binding to each other. In conclusion, this study is the first to show a catalytic mechanism of SETD3-mediated histidine methylation on β-actin, which not only throws light on the protein histidine methylation phenomenon but also facilitates the design of small molecule inhibitors of SETD3.

References

Jul 11, 1991·Nature·J A Theriot, T J Mitchison
Sep 6, 1990·Nature·W KabschK C Holmes
Oct 1, 1967·The Biochemical Journal·P JohnsonS V Perry
Mar 25, 1983·Nucleic Acids Research·U NudelD Yaffe
Feb 1, 1993·Current Opinion in Cell Biology·I M Herman
Apr 17, 2002·Journal of Molecular Biology·Tomas NymanUno Lindberg
Oct 10, 2002·Cell·Raymond C TrievelJames H Hurley
Mar 29, 2003·Physiological Reviews·C G dos RemediosN J Nosworthy
Aug 6, 2003·The Journal of Biological Chemistry·Arnd RichardtBernhard T Hovemann
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Aug 10, 2005·Genome Biology·Shane C DillonXiaodong Cheng
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
May 12, 2010·Nucleic Acids Research·Liisa Holm, Päivi Rosenström
Aug 26, 2010·Cytoskeleton·Benjamin J Perrin, James M Ervasti
Sep 25, 2010·The Journal of Biological Chemistry·Kristofor J WebbSteven G Clarke
Aug 13, 2011·The Journal of Biological Chemistry·Gwang Hyeon EomSang-Beom Seo
Jan 24, 2012·Nature Reviews. Molecular Cell Biology·Eric J Wagner, Phillip B Carpenter
Dec 1, 2012·Current Opinion in Cell Biology·Jonathan R Terman, Anna Kashina
May 24, 2015·The Journal of Biological Chemistry·Jakub DrozakEmile de Heer
Oct 28, 2016·Journal of Synchrotron Radiation·Zhijun WangJianhua He
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor
Apr 10, 2017·FEBS Letters·Virginie F RheinJohn E Walker
Nov 4, 2017·Nature Reviews. Neuroscience·Christophe LeterrierSubhojit Roy
Jul 17, 2018·Current Protocols in Protein Science·Minoru Tamura
Dec 12, 2018·ELife·Sebastian KwiatkowskiJakub Drozak

❮ Previous
Next ❯

Citations

Jun 7, 2020·The Journal of Biological Chemistry·Shaobo DaiXiaodong Cheng
Aug 8, 2019·Nature Communications·Shaobo DaiXiaodong Cheng
Jul 6, 2020·The Journal of Experimental Biology·Cheryl Walker, Warren Burggren
Sep 25, 2020·The Biochemical Journal·Jie GaoZhongliang Zhu
Nov 7, 2020·Biochimica Et Biophysica Acta. Reviews on Cancer·Wen-Jie Shu, Hai-Ning Du
Jan 6, 2021·Nature Chemical Biology·Xinyan ChenChao Xu
Jan 8, 2021·ACS Chemical Biology·Roberto Di BlasiHarry J Whitwell
Feb 1, 2020·Seminars in Cell & Developmental Biology·Anna S Kashina
Mar 20, 2020·Current Protein & Peptide Science·Sebastian Kwiatkowski, Jakub Drozak
May 26, 2021·ChemMedChem·Jordi C J HintzenJasmin Mecinović

❮ Previous
Next ❯

Methods Mentioned

BETA
ubiquitination
enzymatic profiling
PCR

Software Mentioned

iSET
HKL2000
PHENIX
Coot
Prism
Phaser
MicroCal PEAQ - ITC Analysis
DALI
Proteomics Browser
GraphPad

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.