21.6
Protein and Protein Structure
Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins…
Proteins are polymers of amino acids linked together through peptide bonds. Most proteins fold into specific three-dimensional structures to perform their function.
Protein structure is classified into four categories: primary, secondary, tertiary, and quaternary.
The linear sequence of amino acids in the protein is its primary structure. These sequences are read in the polymer synthesis order, from the N-terminal, the free amino end, to the C-terminal, the free carboxyl end.
Secondary structures form through hydrogen bonding between the oxygen from the carbonyl group of one amino acid and the hydrogen from the amino group of another. Common secondary structures include α-helices and β-pleated sheets.
These and other connecting structures, such as β-turns, further interact to form the protein’s three-dimensional structure, known as the tertiary structure.
The formation of the tertiary structure occurs due to interactions between the R-groups of the amino acids.
R-groups with opposite charges can form ionic bonds, and sulfur in two cysteines can form a covalent disulfide bridge. Other contributors include hydrophobic interactions between hydrophobic side chains and hydrogen bonds between polar side chains.
Additionally, some proteins form quaternary structures, assemblies of two or more polypeptide chains. For example, hemoglobin is a protein made up of four subunits, two α and two β.
Scientists can use the structure of a protein to predict its function and location in a cell. Proteins in the cell cytoplasm have hydrophilic amino acids on their surfaces that interact with the water in the cytoplasm and have hydrophobic cores.
In contrast, proteins present in cell membranes often have hydrophobic amino acids on the surface that interact with glycerophospholipids in the membrane and have hydrophilic cores.
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Q1: What are the four levels of protein structure?
Protein structure has four hierarchical levels. Primary structure is the linear sequence of amino acids read from the N-terminal to the C-terminal. Secondary structure forms through hydrogen bonding, creating alpha helices and beta-pleated sheets. Tertiary structure is the three-dimensional shape resulting from interactions between amino acid R-groups. Quaternary structure occurs when multiple polypeptide chains assemble together, as in hemoglobin's four subunits.
Q2: How do amino acids link together to form proteins?
Amino acids are connected by peptide bonds, which form between the carboxyl group of one amino acid and the amino group of the next. This creates a linear polymer chain with a free amino end (N-terminal) and a free carboxyl end (C-terminal). The resulting polypeptide chain can then fold into secondary and tertiary structures through various molecular interactions.
Q3: What causes secondary structures like alpha helices and beta-pleated sheets to form?
Secondary structures form through hydrogen bonding between the carbonyl oxygen of one amino acid and the amino hydrogen of another amino acid in the polypeptide backbone. In alpha helices, these bonds occur between amino acids spaced four residues apart, creating a spiral structure with 3.6 residues per turn. In beta-pleated sheets, hydrogen bonds form between adjacent polypeptide chains aligned parallel or antiparallel to each other.
Q4: What interactions determine a protein's three-dimensional tertiary structure?
Tertiary structure results from interactions between amino acid R-groups. Ionic bonds form between R-groups with opposite charges, while hydrophobic interactions cluster nonpolar R-groups in the protein's interior. Disulfide bridges form covalent bonds between cysteine residues. Hydrogen bonds between polar R-groups also contribute. These combined weak and strong interactions fold the polypeptide into its final three-dimensional shape.
Q5: How does protein location in the cell relate to its amino acid composition?
Protein location depends on the distribution of hydrophilic and hydrophobic amino acids. Cytoplasmic proteins have hydrophilic amino acids on their surfaces to interact with water and hydrophobic cores inside. Membrane proteins have the opposite arrangement: hydrophobic amino acids on the surface interact with glycerophospholipids in the membrane, while hydrophilic amino acids form the core. This arrangement ensures proper protein positioning and function.
Q6: What happens to protein function when its structure changes?
Protein function depends critically on three-dimensional structure. When a protein loses its shape, it becomes nonfunctional. For example, in sickle cell anemia, a single amino acid substitution in hemoglobin's beta chain causes the protein to form long fibers, distorting red blood cells into a sickle shape. This structural change prevents normal oxygen transport and causes serious health complications including breathlessness, dizziness, and pain.
Q7: What is quaternary structure and which proteins exhibit it?
Quaternary structure forms when two or more polypeptide chains assemble into a single functional protein complex. Weak interactions like hydrogen bonds and disulfide linkages stabilize these multi-subunit assemblies. Hemoglobin exemplifies quaternary structure with four subunits: two alpha and two beta chains. Insulin also exhibits quaternary structure through disulfide bonds linking its separate polypeptide chains after post-translational modification.