Testing Your Understanding
About 2-3% of proteins encoded by the human genome are zinc finger proteins. A zinc finger protein has a zinc atom bound to the protein, typically via four amino acids (usually histidine and/or cysteine residues). The amino acids are located on a two stand beta sheet and an alpha helix that together look like two "fingers", with the zinc atom lodged between them. These proteins have a specific affinity and so are very useful in binding to other proteins, DNA, RNA or lipids.
Zinc Finger Motif A typical zinc finger motif is shown here, with beta strands in yellow and the alpha helix in red. The amino acids coordinating the zinc are in CPK, and the zinc atom is brown. (1ZAA.pdb)
GATA-1 and FOG-1 (Friend of GATA) are large zinc finger proteins involved in regulating gene expression by binding to DNA. You will be looking at both the interactions between GATA-1 and FOG-1 and between GATA-1 and DNA.
GATA-1 and FOG-1 are transcription factors that are essential for normal development of embryonic erythrocytes (red blood cells) and megakaryocytes (bone marrow cells responsible for making platelets). In order for correct gene expression to occur FOG-1 must bind to GATA-1 before GATA-1 binds to DNA. Mutation of GATA-1/FOG-1 genes can lead to human blood related diseases.
Both GATA-1 and FOG-1 are zinc finger proteins. That means that they have a zinc atom as part of the structure. The zinc atoms are important to the 3-D structure. Use the buttons below to explore how GATA-1 and FOG-1 coordinate (bind) the zinc atoms. (1Y0J.pdb)
GATA-1 The backbone of GATA-1 is colored orchid. The zinc atom (flashing green and brown) is coordinated — or held in place — by four amino acids, seen here in ball and stick and flashing between purple and cpk.
FOG-1 The backbone of FOG-1 is colored lime green. The zinc atom (flashing green and brown) is coordinated — or held in place — by four amino acids, seen here in ball and stick and flashing between orchid and cpk.
Are the amino acids that coordinate the zinc atom the same in GATA-1 and FOG-1?
What type(s) of interactions occur between the zinc atom and these amino acids?
Click on the following buttons and determine the type of interaction displayed between GATA-1 and FOG-1 . (1Y0J.pdb)
What types of interactions are occurring here – hydrophobic, hydrogen bonds, sulfur-sulfur bond, or salt bridges?
Interactions of GATA-1 with DNA – this is like a right hand holding a rope with the rope being the DNA and the hand being the GATA-1. The GATA-1 carboxyl tail is thought to cause the kink in the DNA to allow the GATA-1 to interact with one of the DNA strands.
Click on the following buttons to determine the types of interactions occurring between GATA-1 and DNA. (2GAT.pdb) The types of nitrogenous bases can be identified by the second letter inside the brackets when you hover over the nucleoside monophosphate. For instance, [DA]124:C.P means that this is adenine. The sugar and phosphate can by identified by the structural position and the last letter can help. For instance, in my earlier example the pointer was hovering over the P for phosphate.
What types of interactions are occurring here?
Click on the following buttons to explore interactions occurring between the phosphate group of the sugar-phosphate backbone on the DNA and the GATA-1. Note that these interactions occur in the minor groove of the DNA. (2GAT.pdb)
What types of interactions are occurring here?
Arginine Residues that Bend DNA Arginine 54 and arginine 56 are displayed here. Note their positions relative to the DNA strand. These two amino acids residues cause the DNA to bend in the direction of the minor groove. This allows the two strands to separate enough for transcription to occur.