Structural Basis for Lower Lysine Methylation State-Specific Readout by MBT Repeats of L3MBTL1 and an Engineered PHD Finger

Journal Article · Wed Sep 17 00:00:00 EDT 2008 · Mol. Cell

DOI:https://doi.org/10.1016/j.molcel.2007.10.023· OSTI ID:1007668

Li, Haitao; Fischle, Wolfgang; Wang, Wooikoon; Duncan, Elizabeth M; Liang, Lena; Murakami-Ishibe, Satoko; Allis, C David; Patel, Dinshaw J ^[1]

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1. MSKCC

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.

• Research Organization: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
• Sponsoring Organization: USDOE
• OSTI ID: 1007668
• Journal Information: Mol. Cell, Vol. 28, Issue (4) ; 11, 2007
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

08 HYDROGEN
36 MATERIALS SCIENCE
AROMATICS
BRAIN
CRYSTAL STRUCTURE
FINGERS
HISTONES
HYDROGEN
ION PAIRS
LYSINE
METHYLATION
NEOPLASMS
PROLINE