Biochemists now know the amino acid sequence for about 65 million proteins, with roughly 1.5 million added each month, and the three-dimensional shape for almost 35,000. Researchers have tried to correlate the primary structure of many proteins with their three-dimensional structure to discover the rules of protein folding. Unfortunately, however, the protein-folding process is not that simple. Most proteins probably go through several intermediate structures on their way to a stable shape, and looking at the mature structure does not reveal the stages of folding required to achieve that form. However, biochemists have developed methods for tracking a protein through such stages and learning more about this important process.
Misfolding of polypeptides in cells is a serious problem that has come under increasing scrutiny by medical researchers. Many diseases—such as cystic fibrosis, Alzheimer’s, Parkinson’s, and mad cow disease—are associated with an accumulation of misfolded proteins. In fact, misfolded versions of the transthyretin protein have been implicated in several diseases, including one form of senile dementia.
Even when scientists have a correctly folded protein in hand, determining its exact three-dimensional structure is not simple, for a single protein has thousands of atoms. The method most commonly used to determine the 3-D structure of a protein is X-ray crystallography, which depends on the diffraction of an X-ray beam by the atoms of a crystallized molecule. Using this technique, scientists can build a 3-D model that shows the exact position of every atom in a protein molecule. Nuclear magnetic resonance (NMR) spectroscopy and bioinformatics (see Concept 5.6) are complementary approaches to understanding protein structure and function.
The structure of some proteins is difficult to determine for a simple reason: A growing body of biochemical research has revealed that a significant number of proteins, or regions of proteins, do not have a distinct 3-D structure until they interact with a target protein or other molecule. Their flexibility and indefinite structure are important for their function, which may require binding with different targets at different times. These proteins, which may account for 20–30% of mammalian proteins, are called intrinsically disordered proteins and are the focus of current research.
Urry, Lisa A.. Campbell Biology. Pearson Education. Kindle Edition. https://www.pearson.com/us/higher-education/series/Campbell-Biology-Series/2244849.html