Examples of Protein-DNA Co-Complexes

This page is a skeletal tutorial on the structures three classes of DNA binding proteins and their interactions with DNA, using the Rasmol program to display three-dimensional structures (here, "PDB files", where PDB = protein data bank format). Rasmol stuff created by Jason Kahn and Hannah Chen from structures and papers from the Pabo, Harrison, and Burley groups.

Key concepts

• Understand the general structural features of protein-DNA complexes and see how the protein recognizes a DNA molecule in a sequence-specific manner.
• Be able to recognize the three classes of DNA binding motifs illustrated here, which are the helix-turn-helix, the zinc finger, and the leucine zipper.

Contents

• This page: directions and sample views (these can be enjoyed without running the viewer program, but you could look at a book instead).
• HTH-DNA PDB file, 1lmb.pdb, the structure of the lambda repressor interacting with DNA by Beamer and Pabo, along with a file of rasmol commands for display of important features. And here is essentially the same content adapted to jmol.
• Zinc finger-DNA PDB file, 1aay.pdb, the structure of the Zif268-DNA complex first crystallized by Pavletich and Pabo and subsequently refined further by Pabo's group, with accompanying command file. Here is a Pymol session (.pse file) that showcases some of the important features. And in jmol (under construction).
• bZIP protein-DNA PDB file, the GCN4 protein by Ellenberger, Brandl, Struhl, and Harrison, with accompanying command file. And here it is in Jmol.
• human TBP-DNA PDB file, from the structure by Nikolov et al. (Burley lab), with accompanying command file. This structure is very similar to yeast and arabadopsis TBP-DNA complexes, including those in multi-protein complexes, solved by several groups. Here is a pymol session file and a movie.
• And here is a link to a separate page on the nucleosome.
• When I create tutorials like this, I work them out by testing commands in the Jmol console (control click in the window to bring up a menu, ten choose Console). Two good sources for syntax are at Sourceforge and St. Olaf's.

Directions (same as for previous DNA tutorial)

1. If you haven't worked out how to use Rasmol, see the Installation Page.
2. Load the molecule of your choice into RasMol (either automatically within Netscape or by hand). The command list includes a line on how to do this but doesn't do it automatically (because of path issues on the Mac).
3. Open the the command list. It might be best to open it as a separate window, which should happen automagically (if not, on the Mac, hold the mouse button down until the menu pops up).
4. Copy and paste from command list file to Rasmol window, or download the file and do it from a text editor (any word processor will do). On Windows, pasting doesn't work and you need to save parts of the file and run them as scripts (use the Notepad). You may need to give a full path for the script name.

Results

Here are gif images generated from the PDB files and scripts above. The images in the left column emphasize the overall structures of the three complexes. The right column shows zoomed-in images of some details of the protein-DNA interactions used in sequence-specific recognition by the three proteins.
Lambda repressor. Note HTH motif, N-terminal arm, symmetric dimer binding successive major grooves of a nearly-symmetric DNA site.	HTH detail. Note the two glutamines H-bonding to each other, specific H-bonds to A, water-mediated bridge to adjacent T, H-bonding of packing helix Gln to phosphate backbone helping to cement recognition helix into the major groove.
Zinc finger-DNA. Note the three alpha helices pointing into the major groove, recognizing 3 bp each. The Zn binding domain is a structural element for protein folding, not directly involved in DNA binding.	Example of a canonical Arginine-Guanine interaction made by the tip of the first finger. Note the buttressing aspartate, which helps position the guanidinium group.
GCN4. Note leucine zipper, basic region, recognition of adjacent major grooves with "chopstick" motif.	GCN4 detail. Note the two symmetry-related asparagines recognizing major groove base pair edges. The script also illustrates an Arg-Gua interaction.
TBP. Note the dramatic DNA bending. The DNA projects toward you on the left, back on the right.	TBP view emphasizing the hydrophobic, relatively flat beta sheet recognition surface.
TBP view emphasizing the minor groove interaction surface and dramatic unwinding.	TBP detail showing one of the Phe intercalation sites on the "stirrups" bending the DNA into the major groove.