Country: United States
Date: May 2005
Why do proteins adopt a particular folded structure?
The way a protein folds (its tertiary structure) is determined by its amino
acid sequence (primary structure) and the laws of thermodynamics (the lowest
energy state). This folding occurs spontaneously as demonstrated by
Christian Anfinsen back in the early 60's. Anfinsen showed that if you heat
denaure (unfold) RNAse by boiling, it loses all its enzyme activity, but if
you allow it to cool gradually, it regains full activity indicating that if
refolds completely on its own, i.e. spontaneously. Anfinsen eventually
received the Nobel prize for his work. If you are wondering where secondary
sructure comes in, for most globular proteins (enzymes, antibodies and
carrier proteins, for example), 90% of their secondary structure is in the
form of an alpha-helix.
Ron Baker, Ph.D.
Proteins are made up of amino acids. There are 20 different amino acids.
Each of the 20 amino acids has a distinct character: some are positively
charged, some negatively charged, some polar, some non polar, etc. The final
shape of a protein is the sum total of all of the interactions among the
different amino acids, and between the amino acids and the surrounding
environment. For example, a non polar amino acid does not interact stably
water, and hence will often be found buried deep within the protein. Charged
amino acids attract others with the opposite charge, while repelling those
with the same charge. Add up all these interactions, and you get the final
folded shape of a protein.
Paul Mahoney, PhD
I'm sure you know that proteins are long chains of amino acids. All amino
acids have 3 basic parts: the amino group, the acid group and a side group.
The amino and acid groups are the same for all amino acids, hence the name.
What makes one different from another is the side group. Side groups can be
positively charged, negatively charged, acidic, basic, hydrophillic (mix
with water) hydrophobic (don't mix with water) and some have sulfur in their
structure. Because they each have unique chemical properties, they can
interact with each other. So DNA directs the order that the amino acids will
come in, and then the side groups start being attracted or repelled by each
other. This causes the protein chain to begin to fold in on itself and take
a three dimensional shape. Since the order of the amino acids determines
which are in proximity to each other and therefore how they will interact,
any change in the order of the amino acids will affect that interaction and
therefore the shape of the protein.
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Update: June 2012