2RHI

Crystal structure of the 3-MBT domain from human L3MBTL1 in complex with H1.5K27me2 at 1.66 angstrom

Summary for 2RHI

• Entry DOI: 10.2210/pdb2rhi/pdb
• Related: 2RHU 2RHX 2RHY 2RHZ 2RI2 2RI3 2RI5
• Descriptor: Lethal(3)malignant brain tumor-like protein, Histone H1.5, TETRAETHYLENE GLYCOL, ... (5 entities in total)
• Functional Keywords: beta barrel, protein-peptide complex, dimethyl-lysine, alternative splicing, chromatin regulator, dna-binding, metal-binding, nucleus, repressor, transcription, transcription regulation, zinc, zinc-finger, transcription-nuclear protein complex, transcription/nuclear protein
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: Q9Y468 P16401
• Total number of polymer chains: 2
• Total formula weight: 40100.86

Authors

Li, H.,Patel, D.J. (deposition date: 2007-10-09, release date: 2007-12-11, Last modification date: 2023-08-30)

Primary citation

Li, H.,Fischle, W.,Wang, W.,Duncan, E.M.,Liang, L.,Murakami-Ishibe, S.,Allis, C.D.,Patel, D.J.
Structural Basis for Lower Lysine Methylation State-Specific Readout by MBT Repeats of L3MBTL1 and an Engineered PHD Finger.
Mol.Cell, 28:677-691, 2007

PubMed 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.

PubMed: 18042461
DOI: 10.1016/j.molcel.2007.10.023

Experimental method

X-RAY DIFFRACTION (1.66 Å)