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Hello. This is Lynne Regan and I'm going to be talking to you about protein design,
in particular folding and design of helical repeat proteins.
I'm going to be using our work on TPRs,
tetratricopeptide repeats to illustrate various aspects of protein design,
and to show with specific examples from our work what we can learn from this approach.
First, I need to just introduce you to
repeat proteins and contrast them with globular proteins.
This first slide, we're looking at four different types of repeat protein;
TPR, HEAT, Leucine rich repeat, Ankyrin repeat.
Which you may well have come across because they're widely distributed throughout nature,
and perform a variety of different functions in a variety of cellular pathways.
And what they typically do is to bind and interact with other molecules,
and aid for complex machines,
and complex arrangements of proteins to perform particular functions.
And it's reasonable to speculate that
their elongated structure helps them to perform these functions,
because it exposes a larger surface area than is possible in globular proteins.
If you look at the green-colored repeat units,
which are evident in the TPR, HEAT,
and Ankyrin repeats particularly,
you'll see that the basic unit is about 20 to 40 amino acids long.
And, to create the protein,
there is a direct repeat in tandem of different numbers of those repeats.
Shown on the picture here are three tandem repeats,
the TPR, many more of the HEAT and five for the Ankyrin repeat.
There are two reasons that we undertake protein design.
One is to better understand the behavior of natural proteins.
If we can recapitulate all the structural and physical properties
of proteins then we really truly understand how they are put together.
This is a kind of a different approach to those in which we take a natural protein,
and so tinker with its structure and properties by making one or two mutations.
This is kind of starting from scratch and building up.
The second reason for undertaking protein design is
to create proteins with novel interesting activities.
And this of course, is a very exciting aspect that we could make
new proteins that will perform new functions and be useful.