3CEY

Crystal structure of L3MBTL2

Summary for 3CEY

• Entry DOI: 10.2210/pdb3cey/pdb
• Descriptor: Lethal(3)malignant brain tumor-like 2 protein (2 entities in total)
• Functional Keywords: mbt, structural genomics, structural genomics consortium, sgc, chromatin regulator, metal-binding, nucleus, transcription, transcription regulation, zinc-finger, transcription regulator
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus (Probable): Q969R5
• Total number of polymer chains: 2
• Total formula weight: 108694.76

Authors

Nady, N.,Guo, Y.,Pan, P.,Allali-Hassani, A.,Qi, C.,Zhu, H.,Dong, A.,Mackenzie, F.,Crombet, L.,Loppnau, P.,Kozieradzki, I.,Vedadi, M.,Edwards, A.M.,Weigelt, J.,Bountra, C.,Arrowsmith, C.H.,Bochkarev, A.,Read, R.,Min, J.,Structural Genomics Consortium (SGC) (deposition date: 2008-02-29, release date: 2008-05-06, Last modification date: 2024-11-13)

Primary citation

Guo, Y.,Nady, N.,Qi, C.,Allali-Hassani, A.,Zhu, H.,Pan, P.,Adams-Cioaba, M.A.,Amaya, M.F.,Dong, A.,Vedadi, M.,Schapira, M.,Read, R.J.,Arrowsmith, C.H.,Min, J.
Methylation-state-specific recognition of histones by the MBT repeat protein L3MBTL2.
Nucleic Acids Res., 37:2204-2210, 2009

PubMed Abstract: The MBT repeat has been recently identified as a key domain capable of methyl-lysine histone recognition. Functional work has pointed to a role for MBT domain-containing proteins in transcriptional repression of developmental control genes such as Hox genes. In this study, L3MBTL2, a human homolog of Drosophila Sfmbt critical for Hox gene silencing, is demonstrated to preferentially recognize lower methylation states of several histone-derived peptides through its fourth MBT repeat. High-resolution crystallographic analysis of the four MBT repeats of this protein reveals its unique asymmetric rhomboid architecture, as well as binding mechanism, which preclude the interaction of the first three MBT repeats with methylated peptides. Structural elucidation of an L3MBTL2-H4K20me1 complex and comparison with other MBT-histone peptide complexes also suggests that an absence of distinct surface contours surrounding the methyl-lysine-binding pocket may underlie the lack of sequence specificity observed for members of this protein family.

PubMed: 19233876
DOI: 10.1093/nar/gkp086

Experimental method

X-RAY DIFFRACTION (2.2 Å)