Modeling Protein Structure

Modeling Protein Structure

Harry S. Truman High School, Bronx

Summer Research Program for Science Teachers

August 2010

Subject: Biology

Aim: How do the properties of amino acids affect the shape of proteins?

Objectives: SWBAT

Explain that amino acids are the building blocks of proteins
Understand that there are 20 different amino acids
Discuss the properties of polar (hydrophilic, negatively charged/acidic or positively charged/basic) and non-polar (hydrophobic, uncharged) side chains (R-groups) of these amino acids have important properties
Demonstrate the secondary folding (alpha helices and beta pleated sheets) and tertiary folding of peptides

Demonstrate that protein tertiary structure is created when the secondary structures fold and form bonds to stabilize the structure into a unique shape

Materials: Mini-Toobers, handout with molecular structure of 20 amino acids, molecular attachments for the Mini-Toober (or colored thumbtacks), scissors

Do Now: Give each student a handout with 6 amino acids. Have students discuss which amino acid R-groups could react with each other by forming bonds. What kinds of bonds? How could these bonds affect the shape of a polypeptide chain?

Lesson Overview: Students work in small groups. Each group will be given a Mini-Toober (available from 3DMolecularDesigns.com) and several attachments representing R-groups of amino acids (e.g. hydrogen molecules, SH groups, polar side chains and non-polar side chains). (Colored thumbtacks can also be substituted to represent these molecules.)

Ask students to fold half the Mini-Toober to create a beta-pleated sheet and the other half to create an alpha helix. Elicit from the class that these secondary structures are created through hydrogen bonds.

Have students arbitrarily place one sulfide molecule on each half of the Mini-Toober and 3 polar and/or non-polar side chains on each half. Fold the two halves of the Mini-Toober to form a tertiary structure. Elicit from the class that our simple model of a tertiary structure is held together by a disulfide bridge. Have students now brainstorm how the other side chains they added will affect the protein’s structure and function. Can any of the additional side chains form bonds with each other, or will they repel each other, and why? What properties do the side chains give the protein? Will it attract water molecules or repel them? Will it be solvent in water?

Then, ask two groups to try to “fit” their proteins together based on the properties of the side chains to create a quaternary structure. How many possible “fits” can they construct, if any?

Discuss how amino acid sequence effects the structure and function of proteins.

Optional: Following this activity, give each group a specific sequence of 6 amino acids to represent on their Mini-Toober. (These amino acids can be on a Xerox handout and students can cut them out with a scissors.) Students must add the appropriate R side chains to their Mini-Toober and then try to fold it to create bonds that make sense (e.g. 2 cysteine molecules would form a disulfide bridge, adjacent glycine and tyrosine R groups may form a hydrogen bond).

Background: (from The Structure of Proteins):

“Proteins are polymers of amino acids covalently linked through peptide bonds into a chain. Within and outside of cells, proteins serve a myriad of functions, including structural roles (cytoskeleton), as catalysts (enzymes), transporter to ferry ions and molecules across membranes, and hormones to name just a few.

“With few exceptions, biotechnology is about understanding, modifying and ultimately exploiting proteins for new and useful purposes. To accomplish these goals, one would like to have a firm grasp of protein structure and how structure relates to function. This goal is, of course, much easier to articulate than to realize! The objective of this brief review is to summarize only the fundamental concepts of protein structure.

Amino Acids
“Proteins are polymers of amino acids joined together by peptide bonds. There are 20 different amino acids that make up essentially all proteins on earth. Each of these amino acids has a fundamental design composed of a central carbon (also called the alpha carbon) bonded to:

a hydrogen
a carboxyl group
an amino group
a unique side chain or R-group

“Thus, the characteristic that distinguishes one amino acid from another is its unique side chain, and it is the side chain that dictates an amino acids chemical properties. Examples of three amino acids are shown below, and structures of all 20 are available. Note that the amino acids are shown with the amino and carboxyl groups ionized, as they are at physiologic pH.

“Except for glycine, which has a hydrogen as its R-group, there is asymmetry about the alpha carbon in all amino acids. Because of this, all amino acids except glycine can exist in either of two mirror-image forms. The two forms – called stereoisomers – are referred to as D and L amino acids. With rare exceptions, all of the amino acids in proteins are L amino acids.

“The unique side chains confer unique chemical properties on amino acids, and dictate how each amino acid interacts with the others in a protein. Amino acids can thus be classified as being hydrophobic versus hydrophilic, and uncharged versus positively-charged versus negatively-charged. Ultimately, the three dimensional conformation of a protein - and its activity - is determined by complex interactions among side chains. Some aspects of protein structure can be deduced by examining the properties of clusters of amino acids. For example, a computer program that plots the hydrophobicity profile is often used to predict membrane-spanning regions of a protein or regions that are likely to be immunogenic.

Peptides and Proteins
“Amino acids are covalently bonded together in chains by peptide bonds. If the chain length is short (say less than 30 amino acids) it is called a peptide; longer chains are called polypeptides or proteins. Peptide bonds are formed between the carboxyl group of one amino acid and the amino group of the next amino acid. Peptide bond formation occurs in a condensation reaction involving loss of a molecule of water.

“The head-to-tail arrangement of amino acids in a protein means that there is a amino group on one end (called the amino-terminus or N-terminus) and a carboxyl group on the other end (carboxyl-terminus or C-terminus). The carboxyl-terminal amino acid corresponds to the last one added to the chain during translation of the messenger RNA.

Levels of Protein Structure
“Structural features of proteins are usually described at four levels of complexity:

Primary Structure: the linear arrangment of amino acids in a protein and the location of covalent linkages such as disulfide bonds between amino acids.
Secondary Structure: areas of folding or coiling within a protein; examples include alpha helices and beta-pleated sheets, which are stabilized by hydrogen bonding, or disulfide bridges, which form between SH groups
Tertiary Structure: the final three-dimensional structure of a protein, which results from a large number of non-covalent interactions between amino
Quaternary Structure: non-covalent interactions that bind multiple polypeptides into a single, larger protein. Hemoglobin has quaternary structure due to association of two alpha globin and two beta globin polyproteins

“The primary structure of a protein can readily be deduced from the nucleotide sequence of the corresponding messenger RNA. Based on primary structure, many features of secondary structure can be predicted with the aid of computer programs. However, predicting protein tertiary structure remains a very tough problem, although some progress has been made in this important area.”

New York City Performance Standards:

S1a, S1b, S1c, S2a, S2d, S4a, S5a, S5c, S6a, S7b, S7c