Crystal Structure of MLL2 Complex Guides the Identification of a Methylation Site on P53 Catalyzed by KMT2 Family Methyltransferases.

Structure
Yanjing LiYong Chen

Abstract

KMT2 family methyltransferases methylate histone H3 lysine 4 and play essential roles in multiple cellular processes. MLL2 (KMT2B) is required for early epigenetic decisions during development and contributes to the methylation of bivalent promoters. Here, we determined the crystal structure of the MLL2SET-RBBP5AS-ABM-ASH2LSPRY complex and confirmed that RBBP5AS-ABM-ASH2LSPRY was essential for activating the MLL2 SET domain through a conserved mechanism across KMT2 family complexes. In the MLL2 complex structure, a short N-terminal loop of MLL2SET adopts a similar configuration of the H3 peptide and inserts into the substrate-binding pocket of another MLL2SET, indicating a potential substrate for MLL2SET. We identify that P53 contains a sequence similar to the N-terminal loop of MLL2SET, and demonstrate that K305 of P53 could be methylated by KMT2 family complexes except for SET1A. Our results provide an important implication of functional interplay between P53 and KMT2 family complexes, and also suggest the possible broad landscape of non-histone substrate for KMT2 family methyltransferases.

References

Jul 20, 1999·Genomics·K T FitzGerald, M O Diaz
Mar 15, 2002·Current Opinion in Genetics & Development·Tony Kouzarides
May 2, 2003·The Journal of Biological Chemistry·Yan-Hsiung WangSheng-Chung Lee
Mar 3, 2004·Acta Crystallographica. Section D, Biological Crystallography·Laurent C StoroniRandy J Read
Nov 2, 2005·Nature Reviews. Molecular Cell Biology·Cyrus Martin, Yi Zhang
Jul 21, 2006·Acta Crystallographica. Section D, Biological Crystallography·Wladek MinorMaksymilian Chruszcz
Aug 1, 2006·Nature Structural & Molecular Biology·Yali DouRobert G Roeder
May 13, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jeongkyung LeeJae W Lee
May 20, 2009·Cell·Jan-Philipp Kruse, Wei Gu
Jun 27, 2009·The Journal of Biological Chemistry·Anamika PatelMichael S Cosgrove
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Aug 13, 2013·Nature Structural & Molecular Biology·Deqing HuAli Shilatifard
May 23, 2015·Nature Reviews. Cancer·Rajesh C Rao, Yali Dou
Aug 1, 2015·Cellular and Molecular Life Sciences : CMLS·Xi ZhangXiaobing Shi
Sep 1, 2015·Structure·Ying ZhangJon R Wilson
Jun 30, 2018·The Journal of Biological Chemistry·Homa RahnamounShannon M Lauberth
Oct 30, 2018·Nucleic Acids Research·John G TateSimon A Forbes
Nov 27, 2019·Current Neurology and Neuroscience Reports·Michael ZechJuliane Winkelmann
Dec 6, 2019·Nature Communications·Sang Ho ParkUhn-Soo Cho
Jan 11, 2020·ELife·Evan J WordenCynthia Wolberger

❮ Previous
Next ❯

Citations

Jan 3, 2021·Journal of Neural Transmission·Paulina Gonzalez-LatapiNiccolò E Mencacci
Dec 12, 2020·International Journal of Molecular Sciences·Elzbieta PorebaJulia Durzynska
Jun 3, 2021·Trends in Pharmacological Sciences·Xiang Zhai, James E Brownell

❮ 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.

Related Papers

Trends in Pharmacological Sciences
Xiang Zhai, James E Brownell
Biochimica Et Biophysica Acta. Gene Regulatory Mechanisms
Kihyun ParkJaehoon Kim
International Journal of Molecular Sciences
Elzbieta PorebaJulia Durzynska
© 2021 Meta ULC. All rights reserved