Jennifer Ekstrom
Assistant Professor
- B.S. 1990, University of Illinois (Urbana-Champaign)
- Ph.D, 1999, Cornell University
- Pfizer Post-doctoral fellow, 1999-2002, Univ of Calif., San Francisco
- Research Scientist, 2002-2003, Structural Biochemistry,Phylos,Inc.
ekstrom@msu.edu
522 Biochemistry Building
Michigan State University
East Lansing, MI 48824-1319
Office: 517-432-8434
Lab: 517-355-1897
Publication search:
Jennifer Ekstrom
Research Interests continued
EZH2 interacts with its partner protein, EED, forming a chromatin-bound PcG complex. The PcG complex modifies the histone tails of chromatin; EZH2 methylates the N-terminal tail of histone H3, while a histone deacetylase (HDAC) associated with EED acetylates the histone H3 tail. EZH2 has no detectable homolog in the PDB by BLAST, PSI-BLAST or consensus fold-recognition servers. Mapping studies have allowed us to focus on the regions involved in the EZH2/EED intermolecular interactions and select useful constructs for crystallization.
Disulfide shuffling & chaperone activity - Protein Disulfide Isomerase
The formation of native disulfide bonds is essential for the folding and stability of many secreted proteins. Protein disulfide isomerase (PDI) is a complex multi-domain enzyme that catalyzes both the formation of disulfide bonds and the re-shuffling of existing disulfide bonds. PDI has an unusually reactive cysteine (pKa 4) that attacks the exposed disulfides of a misfolded protein; the resulting mixed disulfide may then be reshuffled to form a different disulfide bond. Native disulfide bonds are less likely to be attacked by PDI, since they are often buried in stable tertiary structure and, thus, not as easily exposed for attack.
PDI also acts as a general chaperone, binding to misfolded or poorly soluble proteins, even those without disulfide bonds. PDI is found as an integral subunit of several protein complexes such as prolyl-4-hydroxylase and the microsomal triglyceride transferase complex, effectively acting as a “permanent” chaperone for these poorly soluble proteins.
We are determining structures of mammalian PDI with a variety of peptide substrates. Our goal is an understanding how this enzyme binds to unfolded or misfolded proteins and how it catalyzes disulfide formation and exchange in target proteins.