B1.2 Proteins SL & HL
SL Notes
Amino Acids and Proteins
Generalized Structure of an Amino Acid
Amino acids are the monomers that make up proteins.
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There are 20 unique amino acids, each sharing the same general structure:
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A central carbon (alpha (α) carbon) covalently bonded to four different chemical groups:
A carboxyl group (–COOH)
An amino group (–NH₂)
A hydrogen atom (–H)
A unique organic side chain called the R-group
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Each amino acid has a different R-group, which determines its properties.
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R-groups can be non-polar or polar, linear or ringed, giving each amino acid distinct chemical and physical characteristics.
Condensation Reactions: Formation of Dipeptides and Polypeptides
Amino acids join together through a condensation reaction.
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A peptide bond is formed when the carboxyl group (–COOH) of one amino acid reacts with the amino group (–NH₂) of another.
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This reaction releases a water molecule (H₂O) as a by-product.
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The peptide bond is a covalent bond, making it very stable.
Word Equation:
Amino acid + Amino acid → Dipeptide + 1 Water molecule
Formation of Polypeptides
The N-terminus (amino-terminal) is the free amino group not involved in the peptide bond.
The C-terminus (carboxyl-terminal) is the unbound carboxyl group.
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More amino acids can be added by forming new peptide bonds at the C-terminus of the growing chain. Repeated multiple times, forming polypeptides.
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With each new peptide bond, another water molecule is released.
Essential and Non-Essential Amino Acids
Essential amino acids:
Cannot be synthesized by the body and must be obtained from dietary sources.
Essential for growth, maintenance, and tissue repair.
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Non-essential amino acids:
Can be synthesized by the body from other amino acids or protein breakdown.
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A balanced diet is important to obtain necessary proteins.
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Vegans must ensure they consume adequate plant-based protein sources.
Infinite Variety of Peptide Chains
Each protein has a unique sequence of amino acids.
One gene codes for one protein.
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Proteins can have a few to thousands of amino acids in any order.
The proteome is the entire set of proteins in an organism.
Examples of Polypeptides
Amylase – Enzyme that digests starch.
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Lysozyme – Found in tears and saliva, has antibacterial properties.
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Alpha-neurotoxins – Present in snake venom, can bind to and inhibit receptors, causing neurotoxic effects, paralysis, or death.
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Glucagon – Secreted by the pancreas when blood glucose levels are low, stimulating the liver to release stored glucose.
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Myoglobin – Oxygen-binding protein found in muscle tissues.
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Histones – Proteins involved in DNA packaging in eukaryotic chromosomes.
Effect of pH and Temperature on Protein Structure
Protein shape is closely related to function.
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Denaturation:
The structure of a protein is altered, causing it to lose its function, usually permanently.
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Factors affecting protein stability:
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pH changes:
Extreme pH changes alter protein charge, affecting solubility and shape.
This can cause irreversible structural changes, leading to inactivity.
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Temperature changes:
High temperatures break hydrogen bonds, causing the protein to unfold and lose function.
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Denaturation in small proteins may be reversible if the damaging conditions are removed.
B1.2 Proteins
HL notes
Protein’s function is related to its structure
· Proteins perform a wide variety of functions in living organisms, ranging from catalysing chemical reactions to providing structural support.
· The secret to the versatility of proteins lies in the ability of proteins to adopt a vast array of three-dimensional shapes.
Chemical diversity in the R-groups of amino acids
· The R-groups of the amino acids present in a polypeptide determine the properties of the assembled polypeptides.
· R-groups can be hydrophobic or hydrophilic.
· Hydrophobic R-groups are non-polar and tend to repel water molecules.
· Hydrophilic R-groups are polar or charged, acidic or basic, and tend to attract water molecules.
· Polar R-groups contain partial charges that interact with water molecules.
· Charged R groups can be either positively charged (basic) or negatively charged (acidic).
Categories of amino acids found in cell proteins
1. Acidic – having an additional carboxyl group (eg., aspartic acid)
2. Basic – having an additional amino group (eg., lysine)
3. Hydrophilic – have polar or charged R-groups (eg., serine)
4. Hydrophobic – have non-polar R-groups (eg., alanine)
Hydrophobic interaction
· In a folded polypeptide chain, amino acids with hydrophobic R-groups are buried on the inside, to minimize their effect on water molecules.
· This attraction between hydrophobic R-groups, caused by the repulsion of water molecules is called hydrophobic interaction.
· Only polar amino acid side chains tend to be displayed on the outside of a folded protein where they tend to interact with water.
4 levels of protein structure
· primary structure
· secondary structure
· tertiary structure
· quaternary structure.
Primary structure of proteins
· The primary structure of a protein refers to the specific sequence of amino acids that are joined together to form a polypeptide chain.
· The unique sequence of amino acids determines how the polypeptide chain will fold, ultimately leading to the three-dimensional structure of the protein.
· This means that the precise position of each amino acid within the protein structure is critical in determining its shape.
· Changes in the sequence of amino acids may result in significant changes to the protein’s structure and function.
Secondary structure of proteins
· The secondary structure of a protein refers to the local folding patterns that occur within the polypeptide chain
· Two common types of secondary structures are alpha helices and beta-pleated sheets
· This is achieved through hydrogen bonding between the carboxyl group of one amino acid and the amino group of another amino acid in a different part of the polypeptide chain.
· These hydrogen bonds occur in regular positions and help to stabilise and aid in the formation of the secondary structure.
Alpha helices:
· In an alpha helix, the hydrogen bond forms between the amine hydrogen of one amino acid and the carboxyl oxygen of another amino acid that is four residues away in the sequence.
· This repeated pattern of hydrogen bonding allows the polypeptide chain to coil and form the characteristic helical structure.
Beta-pleated sheets:
· Beta-pleated sheets form when sections of the polypeptide chain run parallel to each other, and hydrogen bonds form between adjacent strands.
· These hydrogen bonds create a pleated sheet-like structure, with the individual strands forming the flat surface of the sheet.
Importance of secondary structure
· The ability of polypeptide chains to form pleats and coils through hydrogen bonding plays a crucial role in determining the secondary structure of a protein.
· This, in turn, affects the protein’s overall three-dimensional shape and its ability to perform its specific biological functions.
Super secondary structures
· Patterns adopted by alpha helices and beta pleated sheets
· Examples are four-helix bundle and beta sandwich.
· They form protein domains that are compact, folded structures with a specific function like DNA-binding capability or inducing dimerization between 2 proteins.
· 2 protein monomers form a dimer
Tertiary structure of proteins
· Tertiary structure is the further folding of the polypeptide.
· It is dependent on the interaction between R-groups, which may include the formation of hydrogen bonds, ionic bonds, disulfide covalent bonds and London (dispersion forces).
· These interactions stabilise the structure of the protein.
· The tertiary structure gives rise to the overall three-dimensional shape of the protein.
The tertiary structure of a protein is stabilised by different interactions
Hydrogen bond
· A hydrogen atom is shared by two other atoms.
· Weak bonds, but help to stabilize the protein molecule.
Ionic bond
· In proteins, the R-group can undergo binding or dissociation of hydrogen ions, resulting in a positively or negatively charged state, respectively.
· Electrostatic interaction between oppositely charged ions of different molecules result in ionic bonds.
· May often be broken by changing the pH.
Disulfide covalent bonds
· Strong covalent bond formed by the oxidation of –SH groups of two cysteine side chains.
London (dispersion) forces
· When two or more atoms are very close (0.3-0.4 nm) apart the weakest intermolecular forces occur.
· This leads to hydrophobic interactions.
Effect of polar and non-polar amino acids on tertiary structure of proteins.
· Amino acids with polar R-groups have hydrophilic properties
· Amino acids with non-polar R-groups have hydrophobic properties.
· Compact, folded tertiary conformation exposes hydrophilic surfaces to the solvent and buries hydrophobic residues in the protein’s interior, thereby contributing to protein stability and function.
· Integral proteins have regions with hydrophobic amino acids found inside the membrane and hydrophilic regions are exposed to the cytoplasm or extracellular fluid.
· Fatty acid tails that form the interior of the membrane are non-polar and do not repel the hydrophobic parts of the integral proteins.
· This helps integral proteins to embed in the membrane.
Quaternary structure of proteins
· Arises when 2 or more polypeptide chains or proteins are held together forming a complex, biologically active molecule.
· An example of a protein that has quaternary structure is haemoglobin, which consists of four individual polypeptide chains: two of which are designated ‘ɑ-chains’ and two which are designated ‘β-chains’.
Conjugated proteins
· A combination of protein and non-protein prosthetic group.
· A prosthetic group (non-protein) is a “helper” molecule enabling other molecules to be biologically active.
· E.g. Haemoglobin
Haemoglobin
· Each polypeptide chain in haemoglobin is associated with a non- protein component called haem.
· Haem is a complex molecule (flat molecule of 4 pyrrole groups, held together by = C groups) with iron in its centre.
· The Fe2+ in each haem group can bind reversibly with an oxygen molecule.
Non-conjugated proteins
· Are not associated with prosthetic groups
· Examples are insulin and collagen
Insulin
· Protein hormone involved in glucose regulation
· Composed of 2 chains – an A chain (21 amino acids) and a B chain (30 amino acids)
· A disulphide bond is formed between Cys residues at 6 and 11 in the A chain.
· 2 interchain disulfide bridges are formed between A and B chain to form a combined quaternary structure.
Collagen
· Most abundant fibrous protein in animals
· A substance that gives structure and holds the body together.
· Quaternary structure consists of 3 left-handed helices twisted into a right-handed coil.
· Each helix has the smallest amino acid Gly at every third position with many hydroxyproline and proline residues along the chain.
· This allows each helix to make a turn at every 3rd residue and intertwine around 2 other chains to form a compact triple helix, as glycine is small enough to fit in the center.
· Interchain hydrogen bonds hold the three helices together to form tropocollagen.
· Many triple helices lie parallel in a staggered manner to form fibrils held by covalent bonds neighboring triple helices.
· Fibrils unite to form fibers.
NOS: Observations
· Go through details of X-ray crystallography and cyrogenic electron microscopy on page 220
Fibrous protein
· Tertiary structures that exists as long, coiled chains.
· E.g. collagen found in bones, tendons, muscles and skin.
· Insoluble
· The ends of individual triple helices are staggered, so there are no weak points in collagen fibers, giving it high tensile strength
Globular proteins (spherical shape)
· Highly soluble
· E.g. are enzymes like catalase and lysozyme, hormones like insulin (transported through blood)
· It is synthesized as a preproinsulin molecule of 102 amino acid residues on the ribosomes of the RER of beta cells in the pancreas
· Post-translational modifications in the lumen or ER and GA converts preproinsulin into proinsulin and insulin respectively (refer to Fig., B1.2.24 on page 222)
· This makes insulin a protein that is small and yet stable.
