Proteins, with their multifaceted roles in life processes, exhibit an array of structures. This section delves deeper into the structural details of insulin, collagen, and haemoglobin, elucidating how their unique structures contribute to their specific functions. Moreover, the relevance of protein structures in medical and biotechnological domains is highlighted.
Insulin
Insulin, secreted by the pancreas, plays an essential role in glucose metabolism.
Structure
- Monomeric unit: Insulin comprises two polypeptide chains, A and B, linked by two disulphide bonds.
- A chain: Contains 21 amino acids and has a single internal disulphide bond.
- B chain: Consists of 30 amino acids.
Function
- Primarily responsible for glucose uptake by facilitating its entry into cells.
- Helps in glycogen synthesis, converting excess glucose into glycogen for storage in the liver.
Structure-function relationship
- The disulphide bonds confer stability to the insulin molecule, ensuring its efficacy.
- The separation between the A and B chains is crucial, as alterations here can impact insulin's binding to its receptor.
Structure of insuline. Disulphide bridges shown in yellow (the third disulfide bridge has no role in the linkage).
Image courtesy of AtikaAtikawa
Collagen
Making up a significant portion of our skin, tendons, and bones, collagen is vital for structural integrity.
Structure
- Triple helix: Formed by three polypeptide chains spiralling around each other.
- Glycine residues: Due to its small size, glycine appears every third residue, allowing the chains to pack efficiently.
- Proline and hydroxyproline: These amino acids give the helix its unique kinked shape, aiding in stability.
Function
- Provides structural support to various tissues, making them resilient yet flexible.
- Collagen fibres in bones work in tandem with minerals to handle weight and tension.
Structure-function relationship
- The triple helical nature of collagen makes it incredibly robust, explaining its role in high-stress tissues.
- The specific amino acid sequence, with regular intervals of glycine, ensures tight packing and strength.
Collagen triple helix
Image courtesy of Nevit Dilmen
Haemoglobin
Essential for oxygen transport, haemoglobin fills our red blood cells.
Structure
- Tetrameric protein: It has four polypeptide chains, two alpha (α) and two beta (β).
- Haem groups: Each of the four chains houses a haem group, where iron binds to oxygen.
Function
- Primarily facilitates oxygen transport by binding it in the lungs and releasing it in tissues where needed.
- Assists in carbon dioxide removal, collecting it from tissues and unloading it in the lungs.
Structure-function relationship
- Cooperative binding: The tetrameric structure means that as one oxygen molecule binds, subsequent binding becomes easier, ensuring efficient oxygen pick-up.
- The haem groups in each chain allow for the transport of up to four oxygen molecules simultaneously, optimising oxygen delivery.
Image courtesy of OpenStax College
Medical and Biotechnological Significance of Protein Structures
Disease Understanding
- Misfolded proteins: Many neurodegenerative diseases, like Alzheimer’s and Parkinson’s, are attributed to proteins not folding into their intended structures.
- Mutations in haemoglobin: Specific mutations lead to conditions such as sickle cell anaemia, where the haemoglobin molecules stack incorrectly, deforming red blood cells.
Drug Development
- Insights into insulin's structure paved the way for synthetic insulin variants. Different forms, like rapid-acting or long-lasting, are tailored for individual patient needs.
- Detailed knowledge of protein structures, like enzymes in pathogens, can assist in designing targeted drugs that inhibit pathogenic functions without harming human cells.
Genetic Engineering
- By modifying proteins, scientists can enhance or introduce specific functions. This has massive implications in:
- Agriculture: Crafting plants that are drought-resistant or require fewer pesticides.
- Medicine: Engineering bacteria to produce human proteins, such as insulin, has revolutionised treatment approaches.
Bioinformatics and Structural Biology
- Advanced computing allows scientists to predict protein structures based on their amino acid sequences, a crucial tool in drug design.
- Crystallography and cryo-EM help determine protein structures at atomic resolutions, revealing interaction sites and potential drug targets.
Therapeutic Proteins
- Many modern drugs are proteins, designed to interact in specific ways with other proteins in the body. Examples include monoclonal antibodies used in cancer therapies.
- The biopharmaceutical industry heavily relies on understanding protein structure to design, produce, and validate these therapeutic proteins.
FAQ
The amino acid composition of collagen is pivotal for its structural properties. Notably, every third amino acid residue in collagen is glycine, the smallest amino acid. Its size allows for the tight packing of the three polypeptide chains, ensuring structural compactness. Additionally, the presence of proline and hydroxyproline imparts a distinct kinked shape to the chains, adding to the stability of the triple helix. This specific amino acid arrangement, combined with the triple helix configuration, gives collagen its unmatched tensile strength. It's this strength and resilience, attributed to its amino acid composition, that allows collagen to provide robust structural support in various tissues.
The haem group is a prosthetic group embedded in each of the polypeptide chains of haemoglobin. Central to the haem group is an iron atom, which is precisely where oxygen binds. When oxygen binds to the iron atom, it forms a reversible coordinate covalent bond, allowing haemoglobin to pick up oxygen in the lungs and release it in tissues. The presence of these haem groups in all four chains of haemoglobin means the protein can transport up to four oxygen molecules simultaneously, optimising its efficiency. Without the haem group and its iron atom, haemoglobin would be unable to fulfil its primary role in oxygen transport.
Mutations that alter protein structures can significantly impact their function, leading to diseases. For instance, in sickle cell anaemia, a single amino acid mutation in the beta chain of haemoglobin alters the protein's structure. This results in the haemoglobin molecules stacking together under low oxygen conditions, deforming the red blood cells into a sickle shape, which can block blood vessels and cause pain. In other scenarios, misfolded proteins, due to mutations or other reasons, can aggregate, leading to diseases like Alzheimer’s and Parkinson’s. These aggregated proteins can interfere with cell functions, leading to cell death and the associated symptoms of the diseases.
The presence of both A and B chains in the insulin molecule is paramount for its biological function. These two polypeptide chains are linked by two disulphide bonds, and an internal disulphide bond is also present within the A chain. This arrangement ensures the stability of the insulin molecule. Furthermore, the specific positioning and interaction of the A and B chains facilitate the binding of insulin to its receptor on cell surfaces. A disruption in this configuration, either due to mutations or post-translational modifications, can impair insulin's binding efficiency, which, in turn, may impact its ability to regulate glucose levels effectively in the bloodstream.
To unravel the intricate details of protein structures, scientists rely on advanced technologies. X-ray crystallography, for instance, allows for the determination of protein structures at atomic resolutions. In this technique, proteins are crystallised, and then subjected to X-ray beams. The diffraction patterns produced are then analysed to decipher the protein's structure. Another significant technology is cryogenic electron microscopy (cryo-EM), where samples are flash-frozen and examined under electron microscopes, providing high-resolution images. Moreover, bioinformatics tools enable researchers to predict protein structures based on amino acid sequences. Together, these technologies offer a comprehensive view of protein structures, shedding light on their functions and interactions.
Practice Questions
Collagen, the predominant protein in connective tissues, possesses a unique triple helical structure formed by three polypeptide chains spiralling around each other. This configuration provides immense tensile strength, making collagen incredibly robust. Additionally, the regular presence of glycine, the smallest amino acid, every third residue permits the chains to pack closely, further enhancing the protein's structural stability. Proline and hydroxyproline give the helix its distinct kinked shape, contributing to its stability. Thus, the triple helical structure of collagen, combined with its specific amino acid composition, ensures that it offers the necessary structural support and resilience to tissues such as skin, tendons, and bones.
Haemoglobin is a tetrameric protein consisting of four polypeptide chains: two alpha (α) and two beta (β) chains. Each chain has an embedded haem group, which contains an iron atom capable of binding to an oxygen molecule. This structure allows haemoglobin to carry up to four oxygen molecules simultaneously, optimising oxygen delivery. Moreover, haemoglobin exhibits cooperative binding. When one oxygen molecule binds to a haem group, it induces a conformational change that makes it easier for subsequent oxygen molecules to bind. This ensures efficient oxygen pick-up in the lungs and delivery to tissues, underlining the tight link between haemoglobin's structure and its primary function.
