Understanding Protein Folding and Structure - AP Biology

Chaperonin is the enzyme responsible for folding nascent polypeptide chains into the correct and functional 3-dimensional structure. Lipase is an enzyme that breaks down lipids, or fats. Amylase breaks down starches and complex carbohydrates or sugars. Helicase helps unwind the DNA helix during replication, and topoisomerase II helps keep the DNA untangled and acts as adhesive during DNA repair or replication.

Primary structure revolves around the sequence of amino acids, while secondary structure is achieved through hydrogen bonds interacting along the backbone of the polypeptide. Tertiary structure is achieved through interactions between the various side chains of amino acids and is required for the protein to be functional. Quaternary structure involves the interaction of two or more polypeptide subunits, and adds efficiency to their ability to catalyze a reaction.

Proteins have four levels of structure: primary, secondary, tertiary, and quaternary. These refer to the types of binding and folding that occur in the molecule that cause it to take on a stable shape. Hydrogen bonds occur between parts of the molecule containing slightly positive hydrogen, and other parts that may be slightly negative (generally containing oxygen). These bonds stabilize the protein's secondary structure, allowing more complicated folding into tertiary and quaternary structures. Alpha-helices and beta-pleated sheets form the common secondary protein structures.

Primary structure is driven by peptide bonding, while tertiary structure is derived from disulfide bonds and hydrophobic interactions. Quaternary structure describes the congregation of multiple subunits driven by hydrophobic interaction and protein-mediated assembly.

The formation of -helices and -pleated sheets constitute the secondary structure of a protein. These conformations are reinforced by hydrogen bonds between the atoms in the polypeptide chain.

Primary structure is determined by peptide bonds, which link adjoining amino acids in sequence. Tertiary structure is determined by disulfide bonds between cysteine residues and hydrophobic interactions. Quaternary structure is determined by interactions between multiple subunits of a protein.

Hydrogen bonding is responsible for giving shape to the secondary structures of proteins. The amino acids in the protein all carry carboxyl and amino termini, which are capable of forming hydrogen bonds. Secondary protein structure refers to the formation of alpha-helices and beta-pleated sheets through hydrogen bonding in the amino acid backbone. The R-groups are not involved in secondary structure.

Covalent bonds are used to permanently join atoms together, and are not seen in protein folding. Peptide bonds are a special class of covalent bonds that are responsible for holding the individual amino acids together, forming the protein's primary structure. Ionic bonds are generally formed between metals and non-metals, and are not generally seen in proteins.

Disulfide bridges are formed between the sulfhydryl (-SH) groups of two cysteine residues. These bonds are covalent, and are important in stabilizing the tertiary structure of many proteins.

Quaternary protein structure is distinguished by the fact that several polypeptide chains come together to make a functional protein. This is different than the first three levels of protein structure, which only involve one polypeptide chain. Quaternary structure is held together primarily by hydrophobic interactions between the polypeptide chains (ionic and/or hydrogen bonding is often seen as well). Each polypeptide chain forms a subunit of the protein.

Aggregations of misfolded proteins contribute to degenerative diseases such as Alzheimer’s, Huntington’s, and Parkinson’s diseases. Protein misfolding and degradation lead to protein-related diseases, such as cystic fibrosis.

The generation of new protein begins in the nucleus with the transcription of a gene’s DNA sequence into mRNA. The mRNA is then translated into protein by ribosomes in proximity to the rough endoplasmic reticulum. The rough endoplasmic reticulum functions to accept the growing protein sequence and ensure that it is appropriately folded and modified (i.e. addition of carbohydrate) appropriately. The protein is then transported to the Golgi apparatus for additional maturation of the protein, such as carbohydrate modifications. Lastly, the protein is transported to the cell surface based on signals or motifs in protein sequence that determine where it is transported.

Note that only proteins that are transported in vesicles (i.e. membrane proteins and secreted proteins) require intervention by the rough endoplasmic reticulum and Golgi apparatus. Cytoplasmic proteins can be translated by free-floating ribosomes and folded by chaperone proteins.

Proteins have different levels of structure. Primary structure is the sequence of amino acids, joined by peptide bonds. Secondary structure is determined by hydrogen bonding in the amino acid chain backbone. Tertiary structure is the entire protein's shape, determined by R-group interaction and hydrophobic forces. Quaternary structure is only found in certain proteins, and results from the joining of multiple polypeptide subunits into a functional protein.

Chaperones are proteins that are vital for the proper folding of some polypeptide chains. Without chaperones, proteins may be folded incorrectly and become nonfunctional. Chaperones are particularly essential to tertiary and quaternary structure.

The other answers describe functions of other types of proteins.

Denaturation of a protein means that the structure of the protein has changed, rendering it non-functional. The presence of an enzyme can alter the structure of a substrate protein, but is only likely to affect a small region of the protein structure. In contrast, most denaturing processes involve environmental changes that affect the protein as a whole.

A drop in pH can cause denaturation, as it can de-protonate or re-protonate the protein causing a conformational change. This results in changes in the polar structure of the amino acid and can lead to hydrophobic shifts in tertiary structure to decrease functionality. Change in basicity can cause denaturation for the same reason, since this is essentially an increase in pH. Temperature change can also cause denaturation by disrupting internal bonds of the protein used to create secondary and tertiary structure.

Note that primary structure is not affected by denaturation, which is why proteins can re-fold and regain function after denaturation.

When a point mutation on the DNA strand creates a premature stop codon the RNA template will not be completely translated, resulting in a protein with a lower molecular weight due to fewer amino acid residues. As a result, the protein will also likely be nonfunctional. This is an example of a nonsense point mutation.

A slightly altered protein with the same molecular weight would be an example of a missense point mutation, resulting in the substitution of one amino acid for another.

There are a number of ways that scientists study protein folding and structure. They include the following processes: mutation studies, x-ray crystallography, and spectroscopy. Mutation studies compare the folding patterns of wild type proteins and those with targeted point mutations. X-ray crystallography is a form of high-resolution microscopy that uses x-rays to study the atomic structure of protein crystals through diffraction patterns. Last, a number of spectroscopy methods are employed to study protein folding by comparing unfolded, folded, and partially folded proteins.

There are four levels of protein structure. Primary structure involves the linear arrangement of amino acids. It is simply the linear sequence of amino acids created by the ribosome during translation. Secondary structure involves the hydrogen bonding of the backbone and can form alpha-helices and beta-pleated sheets. Tertiary structure involves the interaction between amino acid side chains, or R-groups. These interactions can be hydrogen bonds, hydrophobic interactions, or disulfide bridges. Quaternary structure involves the interaction between two or more folded subunits, and is not present in every protein structure.

The primary structure of a protein is a linear sequence of amino acids. Amino acids are joined by peptide bonds between the N terminus of one amino acid and the C terminus of another amino acid through a condensation reaction, which results in the release of a water molecule.

The secondary structure of protein folding is two-dimensional and can take two forms: alpha helices and beta-pleated sheets. The secondary structure is characterized by hydrogen bonds between peptide groups.

The tertiary structure of protein folding has a polypeptide chain backbone and a number of protein secondary structures: alpha helices and beta-pleated sheets. The tertiary structure is three-dimensional. The protein folding that causes the formation of the tertiary structure is influenced by hydrophobic interactions, disulfide bridges, hydrogen bonds, and salt bridges that create hydrophobic and hydrophilic regions.

The protein quaternary structure is the highest level of protein architecture and refers to the arrangement of protein subunits and their interactions with one another. There is a range in the complexity in the quaternary structure of proteins from dimers, such as DNA polymerase, to tetramers, such as hemoglobin. These structures are always composed of more than one protein subunit.

Disruption of normal protein folding or denaturation—protein unfolding—occurs under certain environmental conditions. Denaturation is defined as the loss of quaternary, tertiary, and secondary folding through the disruption of protein subunits and bonds. The environmental conditions that cause denaturation include the following: extreme temperatures, chemical interference, and extreme pH levels. Denatured proteins may sometimes refold if conditions stabilize; however, this does not typically happen.