Dive into the complex world of protein structures with a detailed look at the tertiary structure of protein. This in-depth study will elucidate everything you need to know about the tertiary protein structure, from its definition and distinctive features, to the pivotal role it plays in protein function. You will also explore the specific types of bonds found in these structures, and learn about the innovative techniques used to identify them. The topics are illustrated with specific real-life case studies. Essential for chemistry students and biochemistry enthusiasts alike.
Understanding the Tertiary Structure of Protein
The tertiary structure of a protein is a critical concept in biology, owing to the vital roles that these molecular structures play in organism functions. Unlike the linear arrangement of the primary structure or the regular patterns of secondary structures, the tertiary structure of a protein refers to the three-dimensional shape that a single protein molecule attains. This involves further folding and twisting of the secondary structures into a complex shape.
Definitions: What is the Tertiary Structure of a Protein?
The tertiary structure of a protein describes the unique three-dimensional shape of a mature protein molecule that has been assembled from its individual amino acid chains. In this state, the protein can now fulfill its complex biological functions. Achieving the tertiary structure involves complex interactions between amino acids which form specific binding patterns ensuring an efficient and accurate folding process.
Differentiating Primary, Secondary, and Tertiary Structure of Protein
The distinction between the primary, secondary, and tertiary structures of proteins relates to the degrees of complexity and organization of these biomolecules. These variations are crucial for understanding their function within the physiological context.
- Primary Structure: This is the sequence of amino acids that form the polypeptide chain. The sequence is written from the N-terminal to the C-terminal end.
- Secondary Structure: This involves local folding of the polypeptide chain into structures such as alpha helices and beta-pleated sheets. These stable arrangements are held together by hydrogen bonds between adjacent sections of the chain.
- Tertiary Structure: This refers to the complete three-dimensional structure of a protein, resulting from further folding of the secondary structures. The tertiary structure is stabilized by various types of bonds and interactions, including hydrogen bonds, disulfide bridges, and hydrophobic interactions.
Essential Facts about the Tertiary Structure of a Protein
The tertiary structure plays a crucial role in determining the protein's functionality. The specific positioning of different regions of the protein affects its ability to interact with other molecules, substrates, and parts of the cell.
| Fact |
Explanation |
| Proteins need to fold into their tertiary structure to be functional |
Each protein’s specific function requires a precise arrangement in three dimensions, ensured through the protein folding into its tertiary structure. |
| Denaturation affects the tertiary structure |
Heat or chemicals can cause a protein to lose its tertiary structure in a process called denaturation, making it non-functional. |
| Folding is assisted by chaperone proteins |
Protein folding is a complex process and can oftentimes require the help of chaperone proteins that ensure correct folding and prevent aggregation. |
Let's further explore the relevance and the fascinating process of proteomic folding using an example.
Consider the important protein insulin. Insulin starts off as a chain of amino acids–its primary structure. Then it coils into an alpha helix, which is a form of secondary structure. Finally, these helices fold over on themselves into a three-dimensional shape. This shape is attracted to glucose molecules and can bind to them effectively controlling the amount of sugar in the bloodstream. If insulin can't fold properly into its tertiary structure, it can't function, leading to the condition known as diabetes.
Roles and Function of Tertiary Structure of Proteins
Before delving into the specific roles and functions of the tertiary structure of proteins, it's essential to understand that the tertiary structure refers to their unique three-dimensional structure.
The Impact of Tertiary Structure on Protein Function
The tertiary structure has a significant impact on the function of a protein. The three-dimensional shape subtly orchestrated by the protein folding process is central to how a protein interacts with other molecules and performs its functions within the cell. Indeed, the functional diversity of proteins, from acting as enzymes to structural support, is largely due to the diverse shapes they can adopt because of their tertiary structure.
A protein's ability to bind to other molecules, often known as its ligands, is determined by the specific shape and chemical characteristics of the binding pocket, which is formed as part of the tertiary structure. In addition, the movement of other atoms within the protein and the resulting changes in the tertiary structure will often be directly associated with the protein's function.
Specific Functions and Importance of Tertiary Structure of Proteins
The tertiary structure's importance is linked to the specific functions that a protein can perform. A vast range of these functions arises from the protein’s unique shape and the resultant chemical properties. Notably, these include:
- Enzymatic activity: The active site of an enzyme, crucial for its catalytic activity, is a particular three-dimensional pocket shaped during the folding process that forms the tertiary structure.
- Signal transduction: The complex signal networks within cells often rely on proteins changing their shape, i.e., their tertiary structure, in response to specific signals or ligand binding.
- Structural support: Proteins can fulfil a variety of key structural roles within cells and tissues. The strength and flexibility required for such roles are provided by the tertiary structure.
In the context of molecules, a "ligand" refers to an ion or molecule that binds to a central atom to form a coordination complex.
Examples Showcasing the Function of Tertiary Structure of Proteins
To illustrate the relevance of the tertiary structure for protein function, consider two distinctive examples: haemoglobin and myoglobin. Both are oxygen-binding proteins with similar construction but varying functionality, much of which is determined by their tertiary structure.
Take the case of haemoglobin. Its structure consists of four polypeptide chains, each with an individual haem group. The combination of these chains and their arrangement in the tertiary structure allows the haemoglobin to perform its unique function–carrying oxygen throughout the bloodstream. Changing the tertiary structure, for example, by binding oxygen, causes its shape to shift slightly in a process called allosteric regulation, resulting in an improved capacity to bind additional oxygen molecules.
In contrast, myoglobin, whose role is to store oxygen in muscle cells, consists of a single polypeptide chain with a single haem group. Its tertiary structure ensures that myoglobin binds tightly to the oxygen, enabling it to perform its oxygen storage role effectively at the low oxygen concentrations present within muscle cells.
Both haemoglobin and myoglobin provide the perfect illustration of how variations in tertiary structure can lead to different protein capabilities and functions within the organism. Protein dysfunction resulting from errors in achieving the correct tertiary structure is linked to numerous diseases, underscoring the central role of the tertiary structure in protein functionality and, consequently, in organism physiology.
Composition and Bonds found in Tertiary Structure of Protein
The tertiary structure of protein involves a specific arrangement of amino acids and bonding patterns that are critical for the protein’s biological functionality. Among these are peptide bonds, which maintain the primary structure, and additional bonds like hydrogen bonds, disulfide bonds, and ionic bonds, which contribute to the stabilisation and spatial configuration of the tertiary structure.
Understanding the Type of Bonds in Tertiary Structure of a Protein
Proteins have complex structures that are stabilised by an intricate network of bonds. These bonds ensure that the protein's three-dimensional structure remains intact, allowing it to interact suitably with its surroundings and perform its allocated roles. Let's delve deeply into the types of bonds that contribute to the tertiary structure stability.
The Role of Peptide Bonds in Tertiary Structure
At the heart of any protein are peptide bonds. A peptide bond is a chemical bond formed between two amino acids when the carboxyl, or COOH, group of one amino acid reacts with the amino, or NH2 group, of the other. Although a peptide bond holds the primary structure, its role should not be underestimated as it sets up the backbone for the creation of higher-level structures.
A peptide bond is a covalent bond formed between the carboxyl group of one amino acid and the amino group of another amino acid. The elimination of a water molecule accompanies this reaction.
To summarize peptide bonds:
- They are the primary bonds that hold amino acids together in a protein.
- Their arrangement provides a scaffold for the formation of the secondary and tertiary structures.
- The linear sequence of these bonds affects how the protein folds into its final structure.
Hydrogen, Disulfide, and Ionic Bonds in Tertiary Structure of Proteins
In the next level of protein architecture, the tertiary structure, other types of bonds come into play, including hydrogen bonds, disulfide bonds, and ionic bonds.
Hydrogen Bonds
Hydrogen bonds are responsible for the formation of the secondary structures, like the alpha-helix and the beta-sheet. In the tertiary structure, they provide additional stabilisation, especially in parts of the protein where secondary structures meet. Hydrogen bonds in proteins can form between any hydrogen and electron-rich donor atoms such as nitrogen or oxygen.
Hydrogen bonds occur when a hydrogen atom attached to a highly electronegative atom, such as nitrogen, oxygen, or fluorine, experiences the electrostatic field of another nearby electronegative atom.
Disulfide Bonds
Disulfide bonds are unique as they occur between the sulfur atoms of two cysteine residues. Being a covalent bond, a disulfide bond is one of the strongest protein-stabilising bonds, fundamental for maintaining the protein's shape under severe condition changes.
Disulfide bonds are covalent links formed by the oxidation of the sulfhydryl (-SH) groups in the cysteine amino acid residues of proteins.
Ionic Bonds
Ionic or salt bridges are formed between oppositely charged side groups of acidic and basic amino acids. Ionic interactions contribute to protein stability by strongly attracting opposite charges, but are often buried in the protein interior away from water molecules.
Ionic bonds, also known as salt bridges in the context of proteins, are attractions between oppositely charged amino acid residues.
These examples showcase the remarkable complexity of protein folding and highlight how the right sequence of amino acids and the forming of the correct types and number of bonds can have profound implications on how efficiently a protein can perform its function.
Techniques to Identify Tertiary Structure of a Protein
Equally as important as understanding what a protein's tertiary structure is involves the techniques scientists use to identify and examine it. These practices are critical to the broader scope of protein engineering and understanding the function of a molecule in its biological context. There are several techniques for analysing and identifying the tertiary structure of a protein, but among them, X-ray crystallography and nuclear magnetic resonance spectroscopy are the most frequently employed.
Techniques for Identifying and Analysing Protein Structure
The detailed tertiary structure of a protein can be determined through a few different procedures. These sophisticated techniques require complex instrumentation and rigorous computational analysis, but they can provide detailed insights into a protein's structure. The knowledge resulting from these structural studies permits a deeper understanding of how the protein functions and how it interacts with its environment.
It's essential to note that each technique mentioned here primarily focuses on the atomic level to generate an accurate, detailed model of the protein’s tertiary structure.
X-ray Crystallography and Protein Tertiary Structure
When it comes to determining protein structure down to the atomic level, X-ray crystallography is one of the most powerful tools at researchers' disposal. The first step in X-ray crystallography is precipitating the protein into a solid crystal, which is then bombarded with X-ray radiation. As the X-rays pass through and bounce off of the atoms in the crystal, they produce a diffraction pattern. This pattern, which shows the position of the atoms in the protein, is then analysed using computer algorithms to interpret the data, creating a model of protein structure.
However, producing diffraction quality protein crystals can often be a barrier. In some cases, crystal formation is a relatively easy and quick process, but more often, it is a time-consuming task.
Typically, the high-resolution structures achieved make X-ray crystallography the method of choice for protein structure determination, especially when designing therapeutic drugs, where researchers need to know every detail about the target protein's structure.
The first protein structures to be solved were those of myoglobin and haemoglobin in the late 1950s and early 1960s. The work earned a Nobel Prize in Chemistry for John Kendrew and Max Perutz, laying the foundation for the field of structural biology.
Nuclear Magnetic Resonance Spectroscopy and Protein Tertiary Structure
Nuclear Magnetic Resonance (NMR) spectroscopy is another method employed in structural biology to decipher the tertiary structure of proteins. It is an important alternative to X-ray crystallography, especially for proteins that do not crystallise easily. NMR relies on the magnetic properties of certain nuclei and allows proteins to stay in solution, resembling physiological conditions more closely than X-ray crystallography. These characteristics make NMR well suited to studying dynamic phenomena, like protein folding or protein-drug interactions.
Nuclear Magnetic Resonance (NMR) is a research technique that exploits the magnetic properties of certain atomic nuclei. It determines the physical and chemical properties of atoms by detecting the radio frequency absorbed and subsequent relaxation of nuclei in a magnetic field.
However, there are certain limitations to this technique. For instance, NMR cannot be used for very large proteins, as the technique’s complexity increases with the size of the protein. Also, the quality of the information gathered by NMR is highly dependent on the purity of the protein sample, the solubility of the protein, and the conditions of the experiment. Nevertheless, NMR allows one to obtain very rich and detailed information about protein conformational changes and protein-ligand interactions.
Peter Wright and Kurt Wüthrich are two leaders in NMR who have made ground-breaking contributions to the field of protein structure determination using NMR spectroscopy. Wüthrich received the Nobel Prize in Chemistry in 2002 for his work in NMR.
In summary, X-ray crystallography and NMR spectroscopy are two powerful and pioneering techniques used for determining the tertiary structure of proteins. They each have their strengths and limitations but are complementary and vital tools in structural biology, pharmaceutical research, protein engineering, and other scientific areas.
Examples and Illustrations of Tertiary Structure of Protein
The tabletop exploration of the concepts of protein tertiary structure can only take you so far. Sometimes, to truly grasp the depth of these concepts, you need to see how they apply to real-world, tangible examples. This part of our discussion will focus on two widely known proteins: haemoglobin and albumin. By examining the specific tertiary structures of these proteins, you can gain a deeper understanding of how this level of structure contributes to their unique biological functions.
Tertiary Structure of Protein Examples in Biochemistry
The world of biochemistry is filled to the brim with diverse and complicated proteins, each with a unique sequence of amino acids and, therefore, a unique structure. This immense variety enables the wide range of functions that proteins perform in biological systems, from enzymatic activities to structural support and transportation of molecules. For instance, insulin is primarily involved in regulating metabolism, while collagen provides strength and structure to tissues, and antibodies work crucially in the immune response. Despite these functions being incredibly diverse, they all heavily rely on the specific tertiary structure of each protein to function appropriately.
Here, you will explore the tertiary structure of two essential proteins - haemoglobin and albumin - delving into how their structure makes them perfectly suited to their biological roles.
Case Study: Tertiary Structure of Hemoglobin Protein
Haemoglobin is a metalloprotein found in red blood cells, which transports oxygen from the lungs to the rest of the body. Hemoglobin's function is reliant not only on its primary, secondary and tertiary structure, but also on its quaternary structure as it is a tetramer consisting of two alpha and two beta subunits.
The alpha and beta subunits of haemoglobin are remarkably similar in terms of structure. Each subunit has eight alpha-helices, labelled A through H, denoting their presence in the secondary structure. The haem group, which binds to oxygen, is located in a hydrophobic (water-repelling) pocket in each subunit, deeply nestled away from the protein's surface.
A notable feature of haemoglobin's tertiary structure is the essential haem group. The haem is a complex molecule with an iron ion (Fe) at its centre. Oxygen (O2) binds to the iron ion, mediating the critical function of oxygen transport. It is a fascinating example of how even non-peptide units like the metal ion can contribute to a protein's tertiary structure and function.
Case Study: Tertiary Structure of Albumin Protein
The albumin protein is the most abundant protein in human blood plasma, making up approximately half of the plasma protein. It has various functions such as carrying lipids, hormones, and drug molecules around the body, maintaining the body's osmotic pressure (important for water distribution between compartments), and providing a source of endogenous amino acids.
Human serum albumin, often referred to as HSA, is a monomeric multidomain biomolecule, with a total of 585 amino acids in humans. It has a heart shape, where the three domains, I, II, and III, each contain two subdomains A and B, that are structurally similar. These repeated domains consist of multiple alpha-helices and represent a common design within albumin's tertiary structure.
Although albumins do not have a quaternary structure like haemoglobin, their tertiary structure is complex and versatile, allowing them to bind a broad range of endogenous and exogenous substances. Importantly, it is the unfolding and refolding of the alpha-helices within the tertiary structure upon ligand binding that allow albumin to possess its flexible substrate binding.
These two examples of haemoglobin and albumin provide a clear illustration of how understanding the tertiary structure of proteins can provide valuable insights into their functions and mechanisms. It truly underpins the importance of structure-function relationships in the fascinating world of proteins.
Tertiary Structure of Protein - Key takeaways
- The tertiary structure of proteins is their unique three-dimensional structure that impacts their function, including binding to other molecules like ligands.
- The tertiary structure of proteins facilitates various roles such as enzymatic activity, signal transduction, and structural support. For example, insulin's tertiary structure enables it to bind to glucose molecules effectively.
- Several bonding patterns stabilize the tertiary structure of proteins, including peptide bonds, hydrogen bonds, disulfide bonds, and ionic bonds.
- Two significant techniques for identifying the tertiary structure of proteins are X-ray crystallography and nuclear magnetic resonance spectroscopy.
- Examples of proteins showcasing the function of tertiary structure include haemoglobin and myoglobin, the structure of which dictates their unique biological roles.
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