Journal article

The Malignant Brain Tumor Repeats of Human SCML2 Bind to Peptides Containing Monomethylated Lysine

Clara M Santiveri, Bernhard C Lechtenberg, Mark D Allen, Aruna Sathyamurthy, Agnes M Jaulent, Stefan MV Freund, Mark Bycroft

JOURNAL OF MOLECULAR BIOLOGY | ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD | Published : 2008

Abstract

SCML2 (sex comb on midleg-like 2) is a constituent of the Polycomb repressive complex 1, a large multiprotein assembly required for the repression of developmental control genes. It contains two MBT (malignant brain tumor) repeats; the MBT is a protein module structurally similar to domains that bind to methylated histones. We have used NMR spectroscopy to examine the binding specificity of these repeats. Our data show that they preferentially bind histone peptides monomethylated at lysine residues with no apparent sequence specificity. The crystal structure of the complex between the protein and monomethyllysine reveals that the modified amino acid binds to an aromatic rich pocket at one en..

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Grants

Awarded by European Molecular Biology Organization


Awarded by Medical Research Council


Funding Acknowledgements

We thank Mr. K. von Gloss for peptide synthesis and Drs. R. Canales and M. R. Fernandez-Fernandez for advice with peptide purification. We also acknowledge Dr. J. M. Perez-Canadillas for helpful discussions. C.M.S. thanks the European Molecular Biology Organization for funding (ALTF 562-2002).