The Zinc Finger Motif

The zinc finger was the second DNA binding motif whose atomic structure was elucidated. It was known that the protein TFIIIA, a positive regulator of 5S RNA transcription, required zinc for activity. Structural and biophysical analyses revealed that each TFIIIA molecule contains nine zinc ions in a repeating coordination complex formed by closely spaced cysteine-cysteine residues followed 12-13 amino acids later by a histi-dine-histidine pair (Figure 39-14). In some instances— notably the steroid-thyroid receptor family—the His-His doublet is replaced by a second Cys-Cys pair. The protein containing zinc fingers appears to lie on one face of the DNA helix, with successive fingers alternatively positioned in one turn in the major groove. As is the case with the recognition domain in the helix-turn-helix protein, each TFIIIA zinc finger contacts about 5 bp of DNA. The importance of this motif in the action of steroid hormones is underscored by an "experiment of nature." A single amino acid mutation in either of the two zinc fingers of the 1,25(OH)2-D3 receptor protein results in resistance to the action of this hormone and the clinical syndrome of rickets.

Cys-Cys zinc finger Cys-His zinc finger

Figure 39-14. Zinc fingers are a series of repeated domains (two to nine) in which each is centered on a tetrahedral coordination with zinc. In the case of TFIIIA, the coordination is provided by a pair of cysteine residues (C) separated by 12-13 amino acids from a pair of histidine (H) residues. In other zinc finger proteins, the second pair also consists of C residues. Zinc fingers bind in the major groove, with adjacent fingers making contact with 5 bp along the same face of the helix.

Cys-Cys zinc finger Cys-His zinc finger

Figure 39-14. Zinc fingers are a series of repeated domains (two to nine) in which each is centered on a tetrahedral coordination with zinc. In the case of TFIIIA, the coordination is provided by a pair of cysteine residues (C) separated by 12-13 amino acids from a pair of histidine (H) residues. In other zinc finger proteins, the second pair also consists of C residues. Zinc fingers bind in the major groove, with adjacent fingers making contact with 5 bp along the same face of the helix.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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