Our laboratory studies the three-dimensional structure and dynamics of proteins and protein complexes using nuclear magnetic resonance (NMR) spectroscopy. We use the knowledge of structure and dynamics at atomic resolution, combined with other biophysical studies, to elucidate function of biological molecules. Suitable samples for such studies are prepared in our laboratory by implementing tools of molecular biology and biochemistry.

We are currently focusing on structural biology of chromatin. Chromatin is the physiological template of the genetic information in eukaryotes, and is subject to distinct post-translational modifications that occur on histone tails. Chemical modifications such as lysine methylation, lysine acetylation and serine phosphorylation regulate access to the underlying DNA. Dr. C. David Allis has proposed that distinct histone modifications, on one or more tails, act sequentially or in combination to form a histone code that is read by other proteins to bring about distinct downstream events. Chief among these modifications are lysine methylation on residues 4 and 9 of histone H3 tail. These have become epigenetic marks that dictate the transition between transcriptionally active and transcriptionally silent chromatin states. The following selected publications have delineated the molecular recognition of methyllysine 9.

Selected References

Jacobs SA, Khorasanizadeh S. (2002) "Structure of HP1 chromodomain bound to a lysine 9-methylated histone H3 tail." Science. Mar 295(5562):2080-3. Epub 2002 Feb 21. [PubMed]

Jacobs SA, Taverna SD, Zhang Y, Briggs SD, Li J, Eissenberg JC, Allis CD,Khorasanizadeh S. (2001) "Specificity of the HP1 chromo domain for the methylated N-terminus of histone H3." EMBO J. Sep 20(18):5232-41. [PubMed]

Rastinejad F, Wagner T, Zhao Q, Khorasanizadeh S. (2000) "Structure of the RXR-RAR DNA-binding complex on the retinoic acid response element DR1." EMBO J. Mar 19:1045-54. [PubMed]

Khorasanizadeh S, Campos-Olivas R, Summers MF. (1999) "Solution structure of the capsid protein from the human T-cell leukemia virus type-I." J Mol Biol. Aug 291:491-505. [PubMed]