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Proteins are essential for virtually all activities of living organisms, including people.  They are the worker molecules that keep our bodies functioning.  Examples of proteins include hemoglobin (carries oxygen in our blood), the muscle proteins actin and myosin, and enzymes found in the stomach and small intestine that help to digest food.

 
tools

Like familiar tools such as hammers, screwdrivers, and saws, protein molecules have shapes that are adapted to their jobs.  By studying the three-dimensional structures of proteins, HWI scientists are better able to understand how they function normally and how some proteins with abnormal shapes can cause disease.    

beads

Protein Structure

fold
Proteins are large linear molecules composed of small molecules called amino acids that are hooked end-to-end like beads on a necklace.  Twenty standard types of amino acids are commonly found in proteins, and each type has its own characteristic size, shape and chemical properties.  Each different kind of protein has a defined length (ranging from a few to more than 1000 amino acids) and a unique amino acid sequence.  Genes contain the code specifying protein sequences and serve as "instruction manuals" for their manufacture.
A protein molecule does not become active until it twists itself into the proper three-dimensional shape or conformation.  This process is known as protein folding.  Although the final conformation depends only on the amino acid sequence, most proteins require help from other proteins, called chaperones, to fold efficiently.
cork
 

When proteins fold, certain sections assume a spiral or corkscrew shape known as an alpha helix, and other sections form flattened strips known as beta sheets.  These organized parts pack together with other, less organized, regions to form the final, folded protein.

beta  
Scientists still do not understand all the rules by which sequence determines fold.  Therefore, it is necessary to use an experimental technique, such as X-ray diffraction or crystallography, to determine the positions of the atoms in a protein molecule.  (See "Learn More", below.)  Once the atomic positions are known, scientists can use computer graphics programs to make pictures of a molecule and visualize its shape.
Structure and Function

Many proteins function by facilitating chemical reactions.  These proteins, called enzymes, are biological catalysts.  Enzymes often contain a groove or pocket, known as the active site, to hold the molecule (substrate) that they act upon.  Typically, natural selection has honed the shape of the enzyme pocket so that it is complementary to the substrate and highly selective for it.  A lock-and-key analogy is often used to describe the interaction between an enzyme and its substrate.

Many drugs block the interaction of an enzyme with its substrate or with other small molecules or proteins.

 

LEARN MORE
To learn how HWI scientists determine the shapes of protein molecules, go to the section entitled Structural Biology.

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