Design and engineering of zinc-finger domains

Published on October 1, 2007 Updated on April 30, 2017   44 min

Other Talks in the Category: Methods

0:00
In the last couple of decades, there has been a tremendous amount of progress in the design and engineering of a class of protein domain known as zinc fingers. This updated presentation is designed to give you an overview of the field.
0:14
I'll be dividing this talk into five parts. First of all, I'll give you an introduction to naturally occurring zinc fingers, what makes a protein domain a zinc finger, and some of the different types and functions of zinc fingers to give you an idea of the variety that already exists in nature. Then I'll go on to describe some de novo work that is being carried out using zinc fingers, an engineering strategy that have employed to graft desirable features of zinc fingers onto other protein domains. This will be followed up by some basic background on natural zinc finger DNA interactions. That's a lead-up into what has become one of the real success stories in protein design and engineering, which is the designing or engineering of specific DNA binders using polydactyl or poly-zinc finger approaches. I will then finish it up with some recent progress in the development of specific protein-binding zinc fingers to hopefully show you the potential of this small versatile protein domain as protein-binding targets and scaffolds.
1:13
To begin with, let me introduce you to one of my favorite protein domains, the zinc finger. Although, I'm showing you a structure of what most people think of as a zinc finger domain, there are actually a range of different protein domains that are classed as zinc fingers. And you'll be seeing some examples of these in a few minutes. But in general, zinc fingers are small. They're typically less than 100 residues in length and can be as small as about 15 residues. They're also quite rich in cystine and histidine residues. The side chains of these residues are used to ligate zinc II ions, a fairly commonly occurring and quite redox stable metal. And zinc binding is actually essential in order for the zinc finger to fall correctly. In that zinc binding and folding are usually considered to be synonymous in these small protein domains. Zinc fingers are very common eukaryotes. About 3% of the genes within the human genome encode proteins that contain one or more zinc fingers.
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Design and engineering of zinc-finger domains

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