Protein Structure II: Digging Deeper

In the previous post, we discussed the different levels of protein structure.  Here, we will consider more specific details of what makes up protein structure.

Previously, we talked about how secondary structure consists of alpha helices and beta sheets, but there are even more nuanced forms of secondary structure.  For example,  different types of alpha helices exist:  the 3.613 and 310 helices are different types that consist of 3.6 and 3 amino acids per turn of the helix, they also have different radii and lengths.

An interesting little tidbit about alpha helices is that there are certain amino acids that are more likely to be found in helices.  These include alanine, glutamine, leucine, and methionine.  In contrast, there are some amino acids that do not really fit into a helix: proline, glycine, tyrosine, and serine.  These amino acids have structural characteristics (such as proline's "kink") that tend to break helix structure.

Additionally, beta sheets have different properties depending on their orientations.  For example, with a parallel beta sheet, the chains of the protein are oriented in the same direction.  In contrast, anti-parallel beta sheets have chains that run in opposite directions.  See the illustration for a more visual explanation of this trait.

In addition to beta sheets and alpha helices, a few more "secondary structures" exist.  I put this in quotation marks because these types of structures are perhaps not classical structures - in that they're not alpha helices or beta sheets.  The first is the loop, which is a stretch of amino acids that makes a loop - rather self-explanatory!  These loops are important for protein structure because they allow for the creation of relatively compact proteins.  In particular, loops can be found in anti-parallel beta sheets, connecting the two beta strands to make the sheet.  Sometimes these structures are called hairpins because they are tight stretches of amino acids that hold a protein structure together.

The last secondary structural element we'll consider is the crossover loop, which is similar to the hairpin loop, but it connects portions of a protein at a longer distances.  These crossovers can be found especially in anti-parallel beta sheets, connecting the two strands such that they can be anti-parallel.

As mentioned, secondary structure consists of small tracts of protein structure, primarily formed of alpha helices and beta sheets.  These secondary structural elements can be organized into specific combinations called motifs.  Motifs are commonly-found structural organizations in proteins, such as zinc finger or coiled coil motifs.  In the case of a zinc finger motif, there are two beta strands and an alpha helix, making up a fold that looks something like a finger.  Within this motif is a zinc ion, hence its name.  Several proteins contain this motif, which is primarily involved in DNA- and RNA-binding.

Another level of structure is the domain, which is considered a module of a protein.  In general, domains have functions that can be separated from the protein as a whole.  Domains are typically large pieces of proteins (think of them as a swing set on a playground - the playground is for kids to play, and the swing set has its own specific function, to swing!).  An interesting aspect of domains is that they can be found in multiple proteins with similar functions.  For example, some proteins have kinase domains to help with phosphorylation; some have RNA-binding domains; and so on.  By detecting domains within a protein, we can infer its function, and this ability has been incredibly useful in predicting the function of new proteins.

The Basics of Protein Structure Part 1: The Levels of Structure

In a previous post, we had explored the characteristics of the 20 amino acids that make up proteins.  These amino acids make up a diverse collection of molecules that can be strung together, making up proteins that have a multitude of functions within the cell.

Amino acids form a protein through the action of the ribosome, which we will discuss in a future post.  At this time, suffice it to say that the ribosome uses an elegant mechanism to read mRNA and translate it into the protein encoded by the mRNA by adding amino acids in a string.  As this string of amino acids is created, it begins to form a structure that will have functions within the cell.

Four levels of protein structure exist:

Primary (1^o) structure:  The order of the amino acids is the primary structure.  Think of the primary structure as the alphabet of the amino acids: MGRYNVPL, for example.  The primary structure describes what order amino acids are in, and even though it might not seem like very much information, even the primary structure of a protein can provide a great deal of information in terms of its function and its potential 3-dimensional shape.

Secondary (2^o) structure:  When amino acids are polymerized, they form local structures, which make up the secondary structure.  Think of secondary structure as the shape of a group of amino acids.  Two primary forms of secondary structure exist:  alpha helices and beta sheets.  Alpha helices result from the coiling of the amino acid string turning about itself.  In contrast, beta sheets are flatter and lack coiling.  There are several types of alpha helices and beta sheets, which we will save for a future post, and these different types of structures have important implications for overall shape of a protein.

Tertiary (3^o) structure:  Protein structure gets exciting when you talk about tertiary structure, which can be described as the overall three-dimensional shape of a protein.  In general, the tertiary structure is the “final” form of a protein, although modifications on the protein, as well as interactions with other proteins can affect this structure.

Quaternary (4^o) structure:  When proteins interact with each other, they can form complexes, which is the quaternary structure of these proteins.  You can think of this structure as the way proteins contact each other.  The bundling of proteins together can be between proteins of the same type (such as is the case with hemoglobin) or other types of proteins.

The drawing attempts to illustrate the concept of the different levels of protein structure.  Again, think of the primary structure as the order; the secondary structure as the local shape; the tertiary structure as the overall shape; and the quaternary structure as the way this tertiary structure of the protein interacts with other proteins.

How protein structure is established is a fascinating question and a field that is actively studied by prominent labs around the world.  Protein folding is the process of a chain of amino acids curling into its final shape, and how this process occurs is complex and not completely understood.  In general proteins fold depending on their environment (exposed to water or not, for example) and with the help of other proteins, called chaperones.  Protein chaperones help to establish a protein’s structure as well as maintain it during times of stress.  Further, modifications on proteins can change their structures, such as when p53, a protein that is involved in regulating many processes within the cell, is phosphorylated – its structure and, consequently, its function is altered slightly. 

The structure of proteins has fascinated scientists since we first learned about proteins.  Thousands of scientists around the world are still working to discover new structures and to learn how proteins fold.  The science behind protein folding has important implications in diseases such as Alzheimer’s, cancers, and infectious diseases.