6.1 Protein structure and folding
3 min read•august 7, 2024
Proteins are the workhorses of life, and their structure is key to their function. This section dives into the different levels of protein structure, from the basic sequence of amino acids to complex 3D shapes. We'll explore how proteins fold and the forces that hold them together.
Understanding protein structure is crucial for biotech applications like drug design and protein engineering. We'll look at how amino acids link up, form secondary structures, and ultimately create functional proteins. We'll also touch on protein folding and the role of in this process.
Protein Structure Levels
Primary Structure
Top images from around the web for Primary Structure
Protein Structure | Biology for Non-Majors I View original
Is this image relevant?
Proteins · Microbiology View original
Is this image relevant?
File:Protein primary structure.svg - Wikipedia View original
Is this image relevant?
Protein Structure | Biology for Non-Majors I View original
Is this image relevant?
Proteins · Microbiology View original
Is this image relevant?
1 of 3
Top images from around the web for Primary Structure
Protein Structure | Biology for Non-Majors I View original
Is this image relevant?
Proteins · Microbiology View original
Is this image relevant?
File:Protein primary structure.svg - Wikipedia View original
Is this image relevant?
Protein Structure | Biology for Non-Majors I View original
Is this image relevant?
Proteins · Microbiology View original
Is this image relevant?
1 of 3
- Sequence of amino acids linked together by peptide bonds
- Determined by the genetic code and mRNA sequence
- Unique to each protein and essential for its function
- Includes any disulfide bonds between residues
Secondary and Tertiary Structure
- refers to local folding patterns (alpha helices and beta sheets)
- Stabilized by between amino acid backbone groups
- is the overall three-dimensional shape of a single polypeptide chain
- Formed by interactions between side chains of amino acids (hydrophobic, ionic, hydrogen bonding)
- Tertiary structure determines the function of the protein (active sites, binding sites)
Quaternary Structure
- Applies to proteins with multiple polypeptide subunits
- Subunits interact and assemble into a larger functional complex
- Stabilized by the same types of interactions as tertiary structure
- Examples include hemoglobin (4 subunits) and DNA polymerase (multiple subunits)
Amino Acids and Peptide Bonds
Amino Acid Structure and Properties
- Building blocks of proteins consisting of an amino group, carboxyl group, and side chain
- 20 different amino acids with unique side chains that determine their properties
- Side chains can be hydrophobic, hydrophilic, charged, or polar
- Amino acids are linked together by peptide bonds to form polypeptide chains
Peptide and Disulfide Bonds
- Peptide bonds form between the carboxyl group of one amino acid and the amino group of another
- Covalent bonds that are planar and rigid due to resonance stabilization
- Disulfide bonds are covalent linkages between the sulfhydryl groups of cysteine residues
- Provide additional stability to the protein structure (insulin, immunoglobulins)
Secondary Structure Elements
Alpha Helix
- Coiled structure stabilized by hydrogen bonds between the backbone amino and carbonyl groups
- Each turn of the helix contains 3.6 amino acid residues
- Right-handed helix is the most common form found in proteins
- Allows for compact packing of amino acids and is often found in transmembrane proteins
Beta Sheet
- Extended structure formed by hydrogen bonding between backbone groups of adjacent polypeptide strands
- Strands can run parallel or antiparallel to each other
- Beta sheets can be arranged in a barrel-like structure (green fluorescent protein) or a flat sheet (silk fibroin)
- Provides rigidity and stability to the protein structure
Protein Folding and Interactions
Protein Folding Process
- Newly synthesized polypeptide chains fold into their native three-dimensional structure
- Driven by the minimization of free energy and the burial of hydrophobic residues in the core
- Folding pathway involves the formation of secondary structures followed by tertiary interactions
- Misfolding can lead to aggregation and formation of insoluble inclusion bodies
Chaperone Proteins and Folding Assistance
- Chaperone proteins assist in the proper folding of other proteins
- Bind to partially folded or misfolded proteins and prevent aggregation
- Examples include heat shock proteins (Hsp60, Hsp70) and chaperonins (GroEL/GroES)
- Important for maintaining protein homeostasis and preventing protein misfolding diseases
Hydrophobic Interactions
- Tendency of nonpolar amino acid side chains to cluster together in the protein core
- Driven by the entropically favorable release of ordered water molecules around hydrophobic groups
- Major driving force for protein folding and stability
- Disruption of hydrophobic interactions (high temperature, denaturants) leads to protein unfolding
Key Terms to Review (22)
Active site: The active site is a specific region on an enzyme where substrate molecules bind and undergo a chemical reaction. This area is crucial for the enzyme's catalytic activity, as its unique shape and chemical environment facilitate the conversion of substrates into products. The structure and folding of proteins directly influence the formation and functionality of active sites, establishing a connection between protein structure and the biochemistry of enzymes.
Amyloidosis: Amyloidosis is a group of diseases characterized by the abnormal accumulation of amyloid proteins in various tissues and organs, leading to dysfunction and damage. This buildup can interfere with normal organ function, making it a serious health concern. The misfolding of proteins, which is central to amyloidosis, highlights the critical importance of protein structure and folding in maintaining cellular health.
Chaperones: Chaperones are specialized proteins that assist in the proper folding and assembly of other proteins within cells. They play a critical role in ensuring that proteins achieve their functional three-dimensional structures, which is essential for their activity and stability. Without chaperones, proteins can misfold, leading to aggregation or loss of function, which can contribute to various diseases.
Cryoelectron microscopy: Cryoelectron microscopy is a high-resolution imaging technique that allows scientists to visualize the structure of biological macromolecules at very low temperatures. By rapidly freezing samples and using an electron microscope, researchers can capture detailed images of proteins and their complexes in near-native states without the need for crystallization. This method is particularly valuable for studying the intricate details of protein structure and folding mechanisms.
Cysteine: Cysteine is a sulfur-containing amino acid that is crucial in the formation of proteins and plays a significant role in maintaining their structure and function. It contains a thiol (-SH) group, which allows it to form disulfide bonds with other cysteine residues, contributing to the stability and folding of proteins. This ability to create covalent bonds helps in maintaining the tertiary and quaternary structures of proteins, ensuring they can perform their biological functions effectively.
Denaturation: Denaturation refers to the process where proteins or nucleic acids lose their native structure and function due to external stressors such as heat, pH changes, or chemical agents. This alteration disrupts the specific folding and interactions of molecules, leading to a loss of biological activity, which is critical in various biochemical processes.
Disulfide bridges: Disulfide bridges are covalent bonds formed between the sulfur atoms of two cysteine amino acids in a protein, playing a crucial role in stabilizing protein structure. These bonds create links that can help maintain the three-dimensional shape of proteins, influencing their folding and overall stability. Disulfide bridges are particularly important in the context of secreted proteins and those found in harsh environments, where structural integrity is essential for proper function.
Folding pathways: Folding pathways refer to the series of intermediate conformations that a protein undergoes as it transitions from its linear polypeptide form to its final, functional three-dimensional structure. Understanding these pathways is crucial because they highlight how proteins achieve their native state, the role of molecular chaperones in assisting folding, and the potential for misfolding, which can lead to diseases.
Glycine: Glycine is the simplest amino acid, characterized by its single hydrogen atom as its side chain, making it a non-polar and neutral molecule. It plays a crucial role in the structure and function of proteins, serving as a building block for polypeptides and influencing protein folding and stability due to its unique properties. Its small size allows for flexibility in protein structures, which is essential for the formation of various secondary structures like alpha helices and beta sheets.
Hydrogen bonds: Hydrogen bonds are weak attractions that occur between a hydrogen atom covalently bonded to an electronegative atom and another electronegative atom. These interactions play a crucial role in stabilizing the three-dimensional structures of proteins, as they help maintain the proper folding and organization necessary for protein functionality.
Ionic interactions: Ionic interactions are electrostatic forces of attraction between positively and negatively charged ions. These interactions play a crucial role in stabilizing the three-dimensional structure of proteins, influencing their folding and overall stability due to the presence of charged side chains in amino acids that participate in these forces.
NMR Spectroscopy: NMR spectroscopy, or nuclear magnetic resonance spectroscopy, is a powerful analytical technique used to determine the structure of molecules, particularly organic compounds and biomolecules like proteins. It works by exploiting the magnetic properties of atomic nuclei, especially hydrogen and carbon, allowing scientists to observe the local environment of these nuclei within a molecule. This technique is crucial for understanding protein structure and folding, as it provides detailed information about molecular interactions and dynamics.
Phosphorylation: Phosphorylation is a biochemical process that involves the addition of a phosphate group to a molecule, typically a protein, which can alter the protein's function and activity. This modification plays a crucial role in regulating various cellular processes, including signal transduction, metabolism, and cell cycle progression, as it can lead to changes in protein structure and interactions.
Primary structure: Primary structure refers to the unique sequence of amino acids in a protein, determining its fundamental characteristics and functions. This sequence is held together by peptide bonds, forming a polypeptide chain that serves as the basis for higher levels of protein structure, such as secondary, tertiary, and quaternary structures. The order of amino acids in the primary structure directly influences how a protein folds and functions, playing a crucial role in its overall stability and activity.
Prion disease: Prion disease refers to a group of progressive neurodegenerative disorders caused by misfolded proteins known as prions. These abnormal proteins induce normal proteins in the brain to misfold, leading to brain damage and a variety of severe neurological symptoms. The unique aspect of prion diseases is that they are transmissible and can be spread through contaminated tissues or medical procedures.
Proline: Proline is an amino acid that is unique among the 20 standard amino acids due to its distinctive cyclic structure, which makes it a non-essential amino acid. This unique structure gives proline special properties that influence protein folding and stability, making it an important component in the formation of collagen and other structural proteins.
Protein domain: A protein domain is a distinct structural and functional unit within a protein, often responsible for specific biological activities. These domains can fold independently and may exist as stable, functional entities within a larger protein structure, contributing to the overall functionality and diversity of proteins. The modular nature of protein domains allows for the evolution of new proteins through combinations of existing domains, which plays a significant role in the complexity of biological systems.
Proteolysis: Proteolysis is the biological process of breaking down proteins into smaller polypeptides or amino acids through the action of enzymes called proteases. This process is crucial for various cellular functions, including protein turnover, regulation of metabolic pathways, and the activation of certain proteins that are synthesized as inactive precursors. Understanding proteolysis is essential as it directly relates to protein structure and folding, affecting how proteins achieve their functional conformations.
Quaternary structure: Quaternary structure refers to the highest level of protein organization, where multiple polypeptide chains, or subunits, come together to form a functional protein complex. This arrangement is crucial for the protein's overall function and can involve interactions such as hydrogen bonding, ionic interactions, and hydrophobic interactions between the subunits. Understanding quaternary structure is essential for grasping how proteins achieve their final shapes and how those shapes relate to their biological roles.
Secondary structure: Secondary structure refers to the local folding patterns of a polypeptide chain that are stabilized by hydrogen bonds between the backbone amide and carbonyl groups. It is an essential aspect of protein structure, as it influences how proteins achieve their functional forms and how they interact with other molecules. Common types of secondary structures include alpha helices and beta sheets, which play crucial roles in maintaining the overall three-dimensional shape of proteins.
Tertiary structure: Tertiary structure refers to the overall three-dimensional shape of a protein that is formed by the folding and interactions of its secondary structural elements, such as alpha helices and beta sheets. This unique arrangement is stabilized by various types of interactions, including hydrogen bonds, ionic bonds, hydrophobic interactions, and disulfide bridges. The tertiary structure is crucial for the protein's functionality, as it determines how the protein will interact with other molecules and perform its biological roles.
X-ray crystallography: X-ray crystallography is a powerful technique used to determine the atomic and molecular structure of a crystal by measuring the diffraction patterns produced when X-rays are directed at it. This method is crucial in understanding how proteins fold and function, revealing detailed information about their three-dimensional structure, which is essential for studying their biological roles and interactions. Additionally, it plays a significant role in protein purification and characterization by providing insights into purity, structural integrity, and conformational changes.