The L3MBTL3 Methyl-Lysine Reader Domain Functions As a Dimer

ACS Chemical Biology
Brandi M BaughmanStephen V Frye

Abstract

L3MBTL3 recognizes mono- and dimethylated lysine residues on histone tails. The recently reported X-ray cocrystal structures of the chemical probe UNC1215 and inhibitor UNC2533 bound to the methyl-lysine reading MBT domains of L3MBTL3 demonstrate a unique and flexible 2:2 dimer mode of recognition. In this study, we describe our in vitro analysis of L3MBTL3 dimerization via its MBT domains and additionally show that this dimerization occurs within a cellular context in the absence of small molecule ligands. Furthermore, mutations to the first and second MBT domains abrogated L3MBTL3 dimerization both in vitro and in cells. These observations are consistent with the hypothesis that L3MBTL3 engages methylated histone tails as a dimer while carrying out its normal function and provides an explanation for the presence of repeated MBT domains within L3MBTL3.

References

Oct 1, 1980·Biophysical Journal·K E Van HoldeD Lohr
Jan 19, 2000·Nature·B D Strahl, C D Allis
Aug 11, 2001·Science·T Jenuwein, C D Allis
Jun 13, 2002·Proceedings of the National Academy of Sciences of the United States of America·Bradley E BernsteinStuart L Schreiber
Sep 28, 2002·Nature·Helena Santos-RosaTony Kouzarides
Feb 14, 2006·Science·Michael Shogren-KnaakCraig L Peterson
Dec 19, 2006·Nature Reviews. Genetics·Yuri B Schwartz, Vincenzo Pirrotta
Feb 27, 2007·Cell·Tony Kouzarides
Jun 2, 2007·Cell·Patrick TrojerDanny Reinberg
Nov 7, 2007·Nature Structural & Molecular Biology·Sean D TavernaDinshaw J Patel
Sep 26, 2009·Seminars in Cell & Developmental Biology·Roberto BonasioDanny Reinberg
Mar 23, 2011·Journal of Medicinal Chemistry·J Martin HeroldStephen V Frye
Mar 25, 2011·Journal of the American Chemical Society·Cen GaoStephen Frye
Aug 2, 2011·Protein Science : a Publication of the Protein Society·Mary Jane KnightJames U Bowie
Dec 7, 2011·Current Chemical Genomics·J Martin HeroldStephen V Frye
Sep 8, 2012·Journal of Molecular Biology·Nataliya NadyCheryl H Arrowsmith
Jan 8, 2013·Nature Chemical Biology·Lindsey I JamesStephen V Frye
Feb 14, 2013·Clinical Pharmacology and Therapeutics·L I James, S V Frye
Sep 18, 2013·Journal of Medicinal Chemistry·Lindsey I JamesStephen V Frye
Mar 15, 2014·Journal of Medicinal Chemistry·Chakravarthi SimhadriFraser Hof

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Citations

Dec 10, 2015·Biochemistry·Natalia Milosevich, Fraser Hof
Jun 28, 2016·Current Opinion in Chemical Biology·Lindsey I James, Stephen V Frye
Jul 17, 2016·Current Opinion in Chemical Biology·Andrew C RuncieAlessio Ciulli
Sep 1, 2016·Future Medicinal Chemistry·Natalia MilosevichFraser Hof
Jul 10, 2017·Current Opinion in Chemical Biology·Nilesh Zaware, Ming-Ming Zhou

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