Biochemistry I   Spring & Fall Terms

Zif268 Protein-DNA Complex

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  Highlight Interactions:
  1. Overview
  2. Finger 1-bp10
  3. Finger 1-bp8
  4. Finger 2-bp6
  5. Backbone
  6. Zn coordination

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Zif268 Protein-DNA Complex.
Zif268 is a sequence-specific, DNA-binding protein encoded by the human GLI oncogene. This model shows three of the Zif268 zinc fingers as Cartoons with Structure coloring. The DNA is shown as Sticks, colored blue. The Zn2+ atoms (light blue spheres) are numbered in each of the three Zinc Fingers. (cf. Figs. 10.25 and 10.26 in Campbell.)
Choose Rotation from the Chime menu and note the overall similarity between the three Finger-DNA architectures.

The numbered "Highlight Interactions" buttons display the following interactions:
1. Overview of the DNA Base-Specific Recognition: The amino acids that participate in base-specific DNA recognition are labeled and colored CPK. The other protein residues are displayed as Backbone with Structure coloring. The six guanines contacted by the protein are CPK colored. Zoom in to see these interactions in the context of the entire complex.
Alternatively, the next three buttons show details of the isolated base-specific interactions.
2. Finger 1-Base Pair 10: The same interaction is seen in Finger 2 with base pair 7 and in Finger 3 with base pair 4. Arg18 donates two H-bonds to guanine (N7 and O6). Asp20 stabilizes the Arg-guanine contacts. The three Watson-Crick H-bonds are shown as yellow lines.
3. Finger 1-Base Pair 8: The same interaction is seen in Finger 3 with base pair 2. Arg24 donates two H-bonds to guanine (N7 and O6).
4. Finger 2-Base Pair 6: His49 donates one H-bond to guanine (N7). H49 is not involved in Zn2+ binding; those interactions are shown below.
5. DNA Backbone: The side chains that contact the DNA backbone are labeled and colored CPK.
6. Zn2+ coordination in Finger 2: The Cys2-His2 signature sequence binds the Zn in tetrahedral geometry. In addition to its role in coordinating Zn2+, His53 also contacts the DNA phosphate at guanine 4.

This structure is described in:
Pavletich & Pabo (1991) "Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 Å.Science 252 809.    PubMed Abstract.
Additional refinements were published in:
Elrod-Erickson, M., Rould, M. A., Nekludova, L., Pabo, C. O. (1996) "Zif268 protein-DNA complex refined at 1.6 A: a model system for understanding zinc finger-DNA interactions." Structure 4: 1171.     PubMed Abstract.

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