What makes me tick…tock?
Lesson 3: How can genetics change your clock?
June 2012
Protein Structure
The three dimensional structure of proteins is assembled from chains of amino acids folded into
a final functional shape. The structure of the protein determines the interactions of that protein
with other proteins and the ultimate biological function of the protein. In order to function
properly, most proteins require structural properties that allow for dynamic interactions with
various other molecules, including DNA, RNA, other proteins, and even chemicals. Mutations in
protein structure influence the ability of proteins to interact and perform their normal biological
function.
Protein structure is described on four different levels, from the amino acid sequence to the way
that independent amino acid chains assemble into multiple-protein functional units. Primary
structure is the sequence of amino acids joined by peptide bonds, like beads on a string. These
chains of amino acids fold into local patterns based on the interactions of the individual amino
acids in the chain and the environment of the protein; this is referred to as secondary structure.
While the primary sequences of protein vary greatly, the secondary structures of proteins are
relatively conserved. The most common secondary structures are alpha helices and beta sheets.
There are also some parts of many proteins that do not have a set structure—intermolecular
interactions will keep some protein structures
stable, but some areas have variability.
Tertiary structure refers to the overall shape
of the protein and quaternary structure
accounts for how multiple proteins interact to
function together in the cell. Together,
scientists can use information about these
levels of structure to make predictions about
protein function.
Based on the primary structure of a protein,
computational predictions can be made about
the probability of the final secondary and
tertiary structures. By comparing the
predicted structure to other proteins, it is
even possible to hypothesize how an
unknown protein functions in the cell.
However, there are various potential
assembly patterns for any linear sequence, so
it is necessary to determine the shape of a
protein using x-ray crystallography. This
method uses light diffraction patterns from a
protein crystal to determine the three
dimensional structure. This technique can be
difficult, so it is useful to look for common
patterns in the primary structure to predict
how proteins will fold.
A partial rendering of the PER2 protein
structure. The two colors indicate different
domains, or areas, of the protein. The tubes
indicate alpha-helices an the flat arrows
indicate beta-sheets (both secondary
structures). The PER2 gene is responsible for
regulating normal circadian rhythms.
Figure from NCBI protein database; Hennig S,
Strauss HM, Vanselow K, Yildiz O, Schulze S, Arens J,
Kramer A, Wolf E. Plos Biol. (2009) 7 p.E94
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