Abstract
The lysine demethylase JMJD2A has the unique property of binding trimethylated peptides from two different histone sequences (H3K4me3 and H4K20me3) through its tudor domains. Here we show using X-ray crystallography and calorimetry that H3K4me3 and H4K20me3, which are recognized with similar affinities by JMJD2A, adopt radically different binding modes, to the extent that we were able to design single point mutations in JMJD2A that inhibited the recognition of H3K4me3 but not H4K20me3 and vice versa.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 109-111 |
| Number of pages | 3 |
| Journal | Nature Structural and Molecular Biology |
| Volume | 15 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2008 |
| Externally published | Yes |
Bibliographical note
Funding Information:We acknowledge the use of beamlines 19BM and 19ID at Argonne National Laboratory’s Advance Photon Source (APS). We thank Y. Kim and C. Chang at APS for their assistance with X-ray data collection. Use of Argonne National Laboratory Structural Biology Center beamlines at APS is supported by the US Department of Energy, Office of Biological and Environmental Research under contract DE-AC02-06CH11357. This work was supported by grants from the Human Frontier Science Program and from the US National Institutes of Health (CA109449) to G.M.