Jutta Heller, Ph.D.
My graduate work in the laboratory of Dr. Daniel Leahy at the Johns Hopkins University School of Medicine from 1995 – 2001 focused on the study of small modular recognition domains that are involved in the regulation of internal and external cell signaling. We were interested in a particular family of protein-protein binding domains: EVH1 domains. Like SH3 domains, EVH1 domains bind poly-proline sequences within their target proteins. However, the ligand consensus sequences are very different for SH3 and EVH1 domains. In addition, discrete classes of EVH1 domains recognize two related but distinct consensus sequences: PPxxF (where x stands for any amino acid) vs. FPPPP. My crystallographic studies aimed to identify the structural basis of this ligand discrimination among EVH1 domains. While work by others addressed how certain EVH1 domains recognize an FPPPP peptide, it was unknown how the other class of EVH1 domains specifically recognizes the PPxxF sequence. To answer this question we determined the crystal structure of an EVH1 domain in complex with a PPxxF peptide ligand (TPPSPF). To our surprise, the ligand adopted an unusual conformation: the side chains of the Ser-Pro tandem were oriented away from the surface of the protein, explaining the lack of sequence conservation at those two positions in the ligand. By comparing the structures of the two classes of EVH1 domains in complex with their specific targets, we were able to rationalize how regions conserved in one class but not in the other class allow for the observed non-overlapping ligand binding specificities and unique modes of ligand recognition by EVH1 domains.
As a post-doctoral fellow at the University of Chicago from 2001-2004 I was able to build upon my graduate training in molecular and structural biology and expand my interests to include protein-RNA interactions. One area of research in the Correll lab is to address how translation factors (such as EF-G and EF-Tu) and toxins (sarcin and ricin) recognize a universal stem-loop structure in the 23S ribosomal RNA (rRNA) – the sarcin/ricin loop (SRL). Phosphodiester backbone cleavage by sarcin or depurination by ricin of a specific site in the SRL RNA disrupts elongation factor binding to the ribosome, arrests protein synthesis, and ultimately causes cell death. Thus this loop provides an important part of the ribosomal binding site for translational GTPases such as EF-G and EF-Tu. My studies focused on EF-G because it has been shown to bind directly and specifically to a 30-nucleotide mimic of the SRL RNA via gel mobility shift assays. To gain insights into the molecular mechanism of how EF-G recognizes the SRL and how this interaction may be involved in GTP hydrolysis, I attempted co-crystallization of this protein-RNA complex.
• Introduction to Biology I, II and III (TBIOL 120, 130, & 140)
• Human Biology and the Environment (TBIOL 240)
• Genetics and Society (TBIOL 270)
• Molecular Biology (TBIOL 304)
• Foundational Skills in Biomedical Sciences (TBIOMD 310)
• Environmental Science Research Seminar (TESC 310)
• Introduction to Science (TCORE)
• UW-Tacoma Executive Council, 2015-2018
• UW-Tacoma Academic Policy and Curriculum Committee, 2017-2020
- Edwin T. and Vivijeanne F. Sujack Award for Teaching Excellence, Loyola University Chicago College of Arts and Sciences (2010)
- Master Teacher Award, Loyola University Chicago College of Arts and Sciences (2008)
- David E. Rogers Award for Community Service, Johns Hopkins School of Medicine (2001)
|Publication Date||Bibliographic Citation|
Correll, C.C., Yang, X., Gerczei, T., Beneken, J., and Plantinga, M.J. (2004) RNA Recognition and base flipping by the toxin sarcin. J. Synchrotron Rad., 11, 93-96.
Correll, C.C., Beneken, J., Plantinga, M.J., Chan, Y.-L., and Lubbers, M. (2003). The common and the distinctive features of bulged-G motifs based on a 1.04 Å resolution structure. Nucl. Acids. Res., 31, 6806-6818.
Beneken, J., Tu, J.C., Xiao, B., Yuan, J.P., Worley, P.F., and Leahy, D.J. (2000). Structure of the Homer EVH1 Domain-Peptide Complex Reveals a New Twist in Polyproline Recognition. Neuron, 26, 143-154.
Postel, E.H., Weiss, V.H., Beneken, J., and Kirtane, A. (1996). Mutational Analysis of NM23-H2/NDP Kinase Identifies the Structural Domains Critical to Recognition of a c-myc Regulatory Element. Proc. Natl. Acad. Sci. USA, 93, 6892-6897.