|MadSci Network: Biochemistry|
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 form disulfide bonds can influence its ability to generate properly folded proteins.
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