faculty & research

Macromolecular Structure, Function and Dynamics

Joachim Frank investigates the mechanism of translation on the ribosome by using cryo-electron microscopy and single-particle reconstruction. Using these methods, and flexible fitting of X-ray structures, the dynamics of the decoding and translocation mechanisms are revealed. Eric Greene uses a combination of nanofabrication and fluorescence microscopy for visualizing protein-DNA interactions in real time at the single molecule level.  Wayne Hendrickson develops new diffraction methods and uses them to solve structures of proteins involved in signal transduction, viral activity and many other processes.  Barry Honig develops computational approaches for calculating macromolecular electrostatics and its thermodynamic influence on folding and intermolecular interactions. Bioinformatics research includes structure-based sequence analysis, threading, homology model building and databases of protein-protein and protein-ligand interactions. The mechanisms and pathways for ion transport through membranes is studied by Arthur Karlin. Arthur Palmer develops new methods in NMR spectroscopy and uses these methods to study structure and dynamics of macromolecules, particularly the contributions of conformational dynamics to folding, molecular recognition, and catalysis. In addition, programs are being developed for sequence analysis, and exploring evolution. Lawrence Shapiro uses structural information obtained from X-ray crystallography to direct biochemical studies of biological problems, particularly involving neuronal cell adhesion and neural patterning.

Lab Web Sites

bulletJoachim Frank

bulletEric Greene

bulletBarry Honig
bulletArthur Palmer

bulletAlexander Sobolevsky

bulletLawrence Shapiro

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Macromolecular Structure, Function and Dynamics
Dynamics of the tenth type III domain of human fibronectin as represented on a backbone chain trace of the crystal structure 1fna. The 15N order parameters are coded as the width of the backbone worm (increased radii indicate lower order parameters and greater degree of conformational flexibility), and the color coding indicates the presence (yellow) or absence (red) of conformational exchange. The RGD motif, important for interactions with integrins, is colored blue for emphasis. From Carr, P.A. and Palmer, A.G. et. al., Structure 5, 949-959.
Images: Macromolecular Structure, Function and Dynamics
J. A. Butterwick, J. P. Loria, N. S. Astrof, C. D. Kroenke, R. Cole, M. Rance, and A. G. Palmer, Multiple time-scale backbone dynamics of homologous thermophilic and mesophilic ribonuclease HI enzymes, J. Mol. Biol. 339, 855-871 (2004).
Images: Macromolecular Structure, Function and Dynamics
Model for the quaternary ammonium channel blocker binding between channelling helices of the acetylcholine receptor. From Pascual, J.M. and Karlin, A. J. Gen Physiol (1998) 112, 611-621.
Images: Macromolecular Structure, Function and Dynamics
This illustration depicts the mismatch repair protein complex Msh2-Msh6 sliding along DNA and rotating as it tracks the phosphate backbone.
Images: Macromolecular Structure, Function and Dynamics
Cryo-EM map of a complex showing the aminoacyl-tRNA (purple) in the process of entering the E. coli ribosome, still engaged with EF-Tu (red), and stalled by the interference of kirromycin, an antibiotic (not seen). The large subunit is painted blue, the small subunit yellow. tRNAs in the P-site (green) and E-site (orange) positions are also seen. A new method of flexible fitting, Molecular Dynamics-based Flexible Fitting (MDFF), was used to produce the atomic model embedded in the semi-transparent density. MDFF was developed by our collaborator Klaus Schulten (University of Illinois in Urbana-Champaign), employing molecular dynamics simulations (Trabuco et al. K., in press).
Images: Macromolecular Structure, Function and Dynamics
Electrostatic potential (red grid) in the minor groove of DNA in a site that binds Hox protein homeodomains specifically (fkh250) and non-specifically (fkh250^con ). The width of the groove affects the depth of the potential which in turn affects uts ability to bind basic amino acids, two of which bind to the narrow groove of fkh250 but not to the wider groove of fkh250ˆcon.
Images: Macromolecular Structure, Function and Dynamics
Dimer of CD4: a receptor important for entry of HIV into cells. Structure from Wu, H., Kwong, P.D. and Hendrickson, W.A. (1997) 387, 527-530.
Images: Macromolecular Structure, Function and Dynamics
Extracellular domain of a nerve myelin protein placed within a schematic intermembrane region. Shapiro, L and Hendrickson, WA et al, (1996) Neuron 17,435-449.
Images: Macromolecular Structure, Function and Dynamics
Dimer of FHIT: a putative tumor suppressor and dinucleoside polyphosphate hydrolase. Lima, C.D., and Hendrickson, W.A. et al, (1997) Structure 5, 763-774.
Images: Macromolecular Structure, Function and Dynamics
The entry of human immunodeficiency virus (HIV) into cells requires the sequential interaction of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. The crystal structure of gp120 in complex with CD4, and the human antibody 17b revealed this interaction in atomic detail. Depicted here is the HIV gp120 core (red/pink) caught in the act of binding to CD4 (yellow), with the antibody 17b (blue/purple) shown neutralizing gp120 by preventing interactions of the viral envelope with the chemokine receptor. (Reference: P.D. Kwong, R. Wyatt, J. Robinson, R.W. Sweet, J. Sodroski and W.A. Hendrickson. (1998). Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 393, 649-659.)