Part I: Protein Structure.
Ed; 313, 366 + Fig 19.10
Ed.; 319, 380 8
Part II: Cancer.
Ed.; pp. 368-371
Part I: Structural biology
is the branch of biology concerned with figuring out the 3-dimensional
structures of macromolecules.
These days, most work is being done on proteins.
X-ray crystallography (used in the 1950’s to determine the structure of DNA) are very valuable for
determining the structures of proteins even today.
This is because each protein has a different
structure, and it’s not possible to predict the structure of an entire protein by looking at its amino
Proteins often (but not always!) consist of separate domains that fold independently.
cases, these domains are encoded by separate exons.
Each domain can contain combinations of
different secondary structure elements:
These elements are arranged in a
characteristic shape in each type of domain.
That is, the hallmark of each domain is a characteristic
Different domains in one protein can have independent functions.
For instance, one
domain might have enzymatic activity (such as kinase activity), while another domain functions to
bind another protein.
Furthermore, the same domain is often found in different proteins.
proteins can be mix-and-match combinations of different domains.
For instance, “Protein #1” may
consist of 3 domains; A, B, and C.
“Protein #2” may consist of 4 domains; 2 copies of A, B, and D.
In this case, domains A and B are present in both proteins, while domains C and D are only in one
The same domain will have the same overall shape in the different proteins.
example, we’ll be able to recognize a “Domain A” in both Protein #1 and Protein #2.
the amino acid sequences of Domain A in the two proteins will probably be very similar.
Importantly, however, they won’t be identical.
As we’ll see, small changes in the same domain
found in two different proteins can have important consequences for function.
Individual exons can encode discrete domains.
Removal of intervening introns by splicing
joins sequences coding for the different domains, so they’re linked in the final protein.
course of evolutionary time, large-scale chromosomal rearrangements (discussed in the lecture on
mutations) can shuffle different exons in the genome.
As a result, exons that were originally parts
of different genes can be brought together into the same gene, where they might code for different
domains of the same protein.
One way this could occur is by reciprocal translocation (breakage and
rejoining of 2 non-homologous chromosomes to swap the ends), if both chromosomes broke at
points that happened to be in the middle of introns.
Such an event would combine the exons next to
the breakpoints into the same gene, which would now contain exons from both genes.
We’ll look at two examples of common domains, that are both found in many different