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.
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
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
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.
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
that contain one or more zinc fingers.