Structure

Topic: Protein Structure

There are four levels of protein structure (primary, secondary, tertiary, and quaternary) and each successive level ultimately contributes to its shape and function. The shape of a protein is critical to its function because it determines whether the protein can interact with other molecules. o determine how the protein gets its final shape or conformation, we need to understand these four levels of protein structure: primary, secondary, tertiary, and quaternary.

Primary Structure

A protein’s primary structure is the unique sequence of amino acids in each polypeptide chain that makes up the protein. Really, this is just a list of which amino acids appear in which order in a polypeptide chain, not really a structure. As the final protein structure ultimately depends on this sequence, this was called the primary structure of the polypeptide chain. The gene, or sequence of DNA, ultimately determines the unique sequence of amino acids in each peptide chain. A change in nucleotide sequence of the gene’s coding region may lead to a different amino acid being added to the growing polypeptide chain, causing a change in protein structure and therefore function.

Secondary Structure

A protein’s secondary structure is whatever regular structures arise from interactions between neighboring or near-by amino acids as the polypeptide starts to fold into its functional three-dimensional form. Secondary structures arise as H bonds form between local groups of amino acids in a region of the polypeptide chain. Rarely does a single secondary structure extend throughout the polypeptide chain. It is usually just in a section of the chain. The most common forms of secondary structure are the α-helix and β-pleated sheet structures and they play an important structural role in most globular and fibrous proteins.

In the α-helix chain, the hydrogen bond forms between the oxygen atom in the polypeptide backbone carbonyl group in one amino acid and the hydrogen atom in the polypeptide backbone amino group of another amino acid that is four amino acids farther along the chain. This holds the stretch of amino acids in a right-handed coil. Every helical turn in an alpha helix has 3.6 amino acid residues. The R groups (the side chains) of the polypeptide protrude out from the α-helix chain and are not involved in the H bonds that maintain the α-helix structure.

In β-pleated sheets, stretches of amino acids are held in an almost fully-extended conformation that “pleats” or zig-zags due to the non-linear nature of single C-C and C-N covalent bonds. β-pleated sheets never occur alone. They have to held in place by other β-pleated sheets. The stretches of amino acids in β-pleated sheets are held in their pleated sheet structure because hydrogen bonds form between the oxygen atom in a polypeptide backbone carbonyl group of one β-pleated sheet and the hydrogen atom in a polypeptide backbone amino group of another β-pleated sheet. The β-pleated sheets which hold each other together align parallel or antiparallel to each other. The R groups of the amino acids in a β-pleated sheet point out perpendicular to the hydrogen bonds holding the β-pleated sheets together, and are not involved in maintaining the β-pleated sheet structure.

Tertiary Structure

The tertiary structure of a polypeptide chain is its overall three-dimensional shape, once all the secondary structure elements have folded together among each other. Interactions between polar, nonpolar, acidic, and basic R group within the polypeptide chain create the complex three-dimensional tertiary structure of a protein. When protein folding takes place in the aqueous environment of the body, the hydrophobic R groups of nonpolar amino acids mostly lie in the interior of the protein, while the hydrophilic R groups lie mostly on the outside. Cysteine side chains form disulfide linkages in the presence of oxygen, the only covalent bond forming during protein folding. All of these interactions, weak and strong, determine the final three-dimensional shape of the protein. When a protein loses its three-dimensional shape, it will no longer be functional.

R group interactions that contribute to tertiary structure include hydrogen bonding, ionic bonding, dipole-dipole interactions, and London dispersion forces – basically, the whole gamut of non-covalent bonds. For example, R groups with like charges repel one another while those with opposite charges can form an ionic bond. Similarly, polar R groups can form hydrogen bonds and other dipole-dipole interactions. Also important to tertiary structure are hydrophobic interactions (including hydrophobic bonding) in which amino acids with nonpolar, hydrophobic R groups cluster together on the inside of the protein. This leaves hydrophilic amino acids on the outside to interact with surrounding water molecules.

There’s one special type of covalent bond that can contribute to tertiary structure: the disulfide bond. Disulfide bonds, covalent linkages between the sulfur-containing side chains of cysteines that create cystine, are much stronger than the other types of bonds that contribute to tertiary structure. They act like molecular “safety pins” as they keep parts of the polypeptide firmly attached to one another.

Proline induces disruptions to both the α-helix and β-pleated sheet formation due to its physical structure. Proline’s R group binds to the amine group, causing it to be more rigid than the usual amino acid. This binding prevents proline from acting as a hydrogen bond donor. This causes the formation of kinks that disrupt both α-helices and β-pleated sheets.

Quaternary Structure

The quaternary structure of a protein is how its subunits are oriented and arranged with respect to one another. As a result, quaternary structure only applies to multi-subunit proteins; that is, proteins made from more than one polypeptide chain. Proteins made from a single polypeptide will not have a quaternary structure.

In proteins with more than one subunit, weak interactions between the subunits help to stabilize the overall structure. Enzymes often play key roles in bonding subunits to form the final, functioning protein.For example, insulin is a ball-shaped, globular protein that contains both hydrogen bonds and disulfide bonds that hold its two polypeptide chains together. Silk is a fibrous protein that results from hydrogen bonding between different β-pleated chains.

When working out the mass of a protein we need to consider the average molecular weight of an amino acid is 110Da. Dalton (Da) is an alternate name for the atomic mass unit, and kilodalton (kDa) is 1,000 daltons. Some have a higher mass due to their size but this average is used when analysing protein chains. The mass of a protein can be divided by 110Da to work out how many amino acids there are in the chain roughly or the approximated mass of a number of amino acids calculated. For example if a monomer contained 288 amino acids this would have an approximate mass of 31680Da or approximately 32kDa.


Practice Questions

 

Khan Academy

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The electrophoretic separation of proteins

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MCAT Questions

Section Bank B/B Section Passage 3 Question 22


Key Points

Protein structure depends on its amino acid sequence and local, low-energy chemical bonds between atoms in both the polypeptide backbone and in amino acid side chains.

• Protein structure plays a key role in its function; if a protein loses its shape at any structural level, it may no longer be functional.

• Primary structure is the amino acid sequence.

• Secondary structure is local interactions between stretches of a polypeptide chain and includes α-helix and β-pleated sheet structures.

• Tertiary structure is the overall the three-dimension folding driven largely by interactions between R groups.

• Quarternary structure is the orientation and arrangement of subunits in a multi-subunit protein.


Key Terms

antiparallel: the nature of the opposite orientations of the two strands of DNA or two beta strands that comprise a protein’s secondary structure

disulfide bond: A bond, consisting of a covalent bond between two sulfur atoms, formed by the reaction of two thiol groups, especially between the thiol groups of two proteins

primary structure: sequence of amino acids in a polypeptide chain

secondary structure:  local folded structures that form within a polypeptide due to interactions between atoms of the backbone

α helix: the carbonyl (C=O) of one amino acid is hydrogen bonded to the amino H (N-H) of an amino acid that is four down the chain, pulling the chain into a helical structure

β pleated sheet: two or more segments of a polypeptide chain line up next to each other, forming a sheet-like structure held together by hydrogen bonds

tertiary structure: overall three-dimensional structure of a polypeptide

hydrophobic interactions: amino acids with nonpolar, hydrophobic R groups cluster together on the inside of the protein, leaving hydrophilic amino acids on the outside to interact with surrounding water molecules

quaternary structure: how its subunits are oriented and arranged with respect to one another



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