Uniformed Services University of the Health Sciences
Department of Biochemistry and Molecular Biology
4301 Jones Bridge Road, C1094
Bethesda, Maryland 20814-4799
Fax: (301) 295-3512
Lab: (301) 295-3573
Our research spans the fields of biochemistry and biophysics. We are interested in the role of metal ions in protein folding and molecular recognition. To understand these basic phenomena we use a variety of techniques including UV/vis, fluorescence, and CD spectroscopy, microscopy, X-ray based techniques, and NMR methods. Currently, work in our lab is divided between two areas of interest: host cell:HIV interactions and peroxisomal protein targeting.
Vif is a 23 kD accessory protein that promotes the ubiquitination and proteasomal degradation of Apo3G, a cellular cytidine deaminase. Interaction of Vif with a Cullin 5 (Cul5)-based E3 ligase is required for Apo3G degradation and recent studies suggest that a conserved HCCH motif plays a vital role in the Vif-Cul5 interaction (Xiao et al.; Mehle et al., 2006). We are using several biochemical and biophysical approaches to unravel the mechanism of Vif.
Peroxisomes are found in eukaryotes. Peroxisomal targeting signal-1 (PTS1) is a conserved tripeptide that is found at the C-terminus of more than 95% of all known peroxisomal matrix proteins. Pex5 is the PTS1 receptor and contains 7 conserved tetratricopeptide repeat (TPR) domains at its C terminus. We are studying how PTS1 binding to Pex5 is signaled to other downstream components (Pex14, Pex10, and Pex12) of the import machineryPEX. Recent structural work suggests that a key to the Pex5 mechanism involves intrinsic disorder in Pex5. We are studying molecular dynamics in the N- and C-termini of Pex5 using fluorescence techniques.
Maynard E.L. and Berg J.M. "Quantitative Analysis of Peroxisomal Targeting signal Type-1 Binding to Wild-type and Pathogenic Mutants of Pex5p Supports an Affinity Threshold for Peroxisomal Protein Targeting" 2007 J. Mol. Biol., 368(5):1259-1266
Paul, I., Cui, J., and Maynard E.L. "Zinc Binding to the HCCH Motif of HIV-1 Vif Induces a Conformational Change that Mediates Protein-Protein Interactions" 2006 Proc. Nat. Acad. Sci. USA 103:18475
Ernest Maynard, Ph.D. (Principal Investigator)
Kalyan Giri, Ph.D. (Research Fellow)
Indrani Paul, Ph.D. (Research Fellow))
Rachael Nhan, (MCB student))
Jian Cui (Summer student))
Stephanie Ford-Molvik (EID, USUHS))
Kenny Lin (EID, USUHS))
Ankush Jain (Medical Student))
Sparsh Gola (Montgomery Balir HS)