MadSci Network: Biochemistry

Re: What causes variation in protein structure?

Date: Thu Dec 30 11:56:26 2004
Posted By: Kurt Wollenberg, Assistant Professor, Ophthalmology and Medicine
Area of science: Biochemistry
ID: 1102043879.Bc

Because protein structure is the result of interactions among the
constitutent amino acids and the environment (usually water) and the amino
acids are specified by sequence of nucleotides in the DNA, variation in
structure can be traced to variation in the DNA sequence. However, it is
not always the case that structural variants are due to changes in the
nucleotides coding for the specific amino acids. Because the DNA is
transcribed into mRNA and the mRNA is processed (usually by the removal of
intron sequence) before being translated into protein there are other
routes to variation in protein structure. Sometimes introns that are
normally excised are kept for translation or exons that are normally used
in translation are excised with their surrounding introns. In these two
instances changed proteins arise that are called splice variants. Splice
variants will have many of the same structural constituents as the "normal"
protein but will either be missing pieces or have extra structures. This is
different from the type of variation that occurs when a specific amino acid
is replaced by one with different chemical proerties, which in turn can
change aspects of the surrounding structure (such as disrupting a helix or
causing two areas of the protein that are normally close together to be
held apart). Structural variants will occur over evolutionary time when DNA
substitutions that code for changes in amino acid sequence arise and are
maintained in a population through deterministitic forces (such as
selection) or stochastic events (such as genetic drift). Splice variants
tend to exist at the same time in the same individual or cell and their
presence can be influenced by the environment or possibly due to chance
(for example, over thousands of mRNA processing events there is a
reasonable probability that a specific intron will be kept in the mRNA).

Moderator's Note: In addition to the mechanisms that Kurt has
described here, different tertiary and quaternary protein structures can 
be observed for proteins with identical primary (peptide) sequences as
a result of differences in the mechanisms of protein folding, as in the 
case of prions.
In addition, variation in a cell's ability to 
disulfide bonds can influence its ability to generate properly folded proteins.

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