Structural basis for lower lysine methylation state-specific readout by MBT repeats of L3MBTL1 and an engineered PHD finger Journal Article

   

Authors:	Li, H.; Fischle, W.; Wang, W.; Duncan, E. M.; Liang, L.; Murakami Ishibe, S.; Allis, C. D.; Patel, D. J.
Article Title:	Structural basis for lower lysine methylation state-specific readout by MBT repeats of L3MBTL1 and an engineered PHD finger
Abstract:	Human L3MBTL1, which contains three malignant brain tumor (MBT) repeats, binds monomethylated and dimethylated lysines, but not trimethylated lysines, in several histone sequence contexts. In crystal structures of L3MBTL1 complexes, the monomethyl- and dimethyllysines insert into a narrow and deep cavity of aromatic residue-lined pocket 2, while a proline ring inserts into shallower pocket 1. We have also engineered a single Y to E substitution within the aromatic cage of the BPTF PHD finger, resulting in a reversal of binding preference from trimethyl- to dimethyllysine in an H3K4 sequence context. In both the "cavity insertion" (L3MBTL1) and "surface groove" (PHD finger) modes of methyllysine recognition, a carboxylate group both hydrogen bonds and ion pairs to the methylammonium proton. Our structural and binding studies of these two modules provide insights into the molecular principles governing the decoding of lysine methylation states, thereby highlighting a methylation state-specific layer of histone mark readout impacting on epigenetic regulation. © 2007 Elsevier Inc. All rights reserved.
Keywords:	unclassified drug; methylation; brain tumor; neoplasm proteins; nerve tissue proteins; structure-activity relationship; tyrosine; transcription factors; dna; amino acid sequence; molecular sequence data; kinetics; histone; peptides; crystal structure; hydrogen bond; models, molecular; crystallography, x-ray; protein structure, tertiary; dna mutational analysis; mutant proteins; glutamic acid; histones; lysine; proline; carboxylic acid; genetic regulation; antigens, nuclear; repetitive sequences, amino acid; protein l3mbtl1; protein engineering; methylammonium; protein phd
Journal Title:	Molecular Cell
Volume:	28
Issue:	4
ISSN:	1097-2765
Publisher:	Cell Press
Date Published:	2007-11-30
Start Page:	677
End Page:	691
Language:	English
DOI:	10.1016/j.molcel.2007.10.023
PUBMED:	18042461
PROVIDER:	scopus
PMCID:	PMC4689580
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-36249026356&partnerID=40&md5=59e6f3e39f3c711b30d45ae191f55677
Notes:	--- - "Cited By (since 1996): 57" - "Export Date: 17 November 2011" - "CODEN: MOCEF" - "Source: Scopus"

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