B1.2 Proteins

Proteins connect amino acid structure, peptide-bond formation, dietary requirements, folding levels, R-group chemistry, denaturation, and functional protein shapes in cells.

Learning objectives

B1.2.1Generalized amino acid structure• Amino acids have an alpha carbon bonded to an amine, carboxyl, hydrogen, and R-group• The R-group varies between amino acids and determines chemical properties• Proteins contain C, H, O, N, and usually S B1.2.2Condensation reactions• Condensation joins the carboxyl group of one amino acid to the amine group of another• A peptide bond forms and water is released• Chains have an N-terminus and C-terminus and are assembled at ribosomes B1.2.3Dietary amino acids• Essential amino acids cannot be synthesized and must be obtained from dietary protein• Non-essential amino acids can be made by transamination, mainly in the liver• Deficiency of essential amino acids limits protein synthesis and can cause malnutrition B1.2.4Infinite variety of peptide chains• Twenty coded amino acids can form vast numbers of sequences• Protein diversity depends on amino acid type, number, and order• Genes encode polypeptide sequences; the proteome is the full protein set expressed B1.2.5Effect of pH and temperature• Protein shape determines function, especially enzyme active sites• High temperature or unsuitable pH disrupts weak bonds and denatures proteins• Denaturation may be reversible in small proteins but often becomes irreversible B1.2.6(HL)—Chemical diversity in R-groups• R-groups may be acidic, basic, polar hydrophilic, or non-polar hydrophobic• R-group chemistry determines solubility, interactions, folding, and function• Hydrophobic R-groups are often buried away from water in soluble proteins B1.2.7(HL)—Primary structure impact• Primary structure is the ordered amino acid sequence joined by peptide bonds• The sequence is controlled by DNA via mRNA• A single amino acid change can alter conformation and protein properties B1.2.8(HL)—Secondary structure• Secondary structure forms when local regions coil or pleat• Alpha helices and beta-sheets are stabilized by regular hydrogen bonding• These structures can combine into domains such as coiled coils or beta sandwiches B1.2.9(HL)—Tertiary structure• Tertiary structure is the unique 3D folding of one polypeptide• R-group interactions stabilize the shape• Hydrogen bonds, ionic bonds, disulfide covalent bonds, and hydrophobic interactions are key B1.2.10(HL)—Effect of polar/non-polar amino acids• Soluble globular proteins often fold with hydrophobic residues in the core• Polar and charged residues are commonly exposed to water• Integral membrane proteins have hydrophobic regions facing lipid tails and hydrophilic exposed regions B1.2.11(HL)—Quaternary structure• Quaternary structure joins two or more polypeptide chains into one functional protein• Haemoglobin is conjugated: four globin chains plus haem groups with iron• Insulin and collagen are non-conjugated examples stabilized by disulfide bonds or triple helices B1.2.12(HL)—Globular vs. fibrous proteins• Globular proteins are compact, often soluble, and suited to transport, signalling, or catalysis• Insulin is a small globular hormone stabilized by disulfide bridges• Fibrous proteins such as collagen are long, insoluble, and provide tensile strength

Every protein amino acid has an α-carbon bonded to an amine group, a carboxyl group, a hydrogen atom and a variable R-group. The shared groups form peptide bonds; the R-group changes charge, polarity, size and reactivity. Proteins contain C, H, O and N, and usually S in sulfur-containing R-groups.

Clean mobile-friendly diagram of a generalized amino acid with a central alpha carbon and labelled amine group, carboxyl group, hydrogen, and R-group. Add a small note that sulfur is present in some amino acids and therefore in many proteins.

Amine and carboxyl groups: shared parts that build the repeating backbone.
R-group: variable part that changes interactions, folding and function.
Proteins contain C, H, O and N; sulfur occurs in proteins with sulfur-bearing R-groups.

The diagram shows two amino acids forming a dipeptide through a condensation reaction, producing a peptide linkage and water.

The carboxyl group of one amino acid loses OH and the amine group of another loses H. Water is released, and the remaining carbon and nitrogen form a covalent C–N peptide bond.

Two residues form one peptide bond and release one water molecule; joining $n$ residues forms $n-1$ peptide bonds and releases $n-1$ waters. Ribosomes repeat this reaction to assemble a chain with N- and C-termini.

Category	Supply to the body
Essential	cannot be synthesized in sufficient quantity; must come from food
Non-essential	can be produced from other molecules, often by transamination in the liver

Dietary protein → digestion → absorbed amino acids → amino-acid pool → ribosomes. If one required essential amino acid is scarce, it becomes limiting and synthesis of proteins containing it slows even when other amino acids are abundant.

A varied, sufficient plant-based diet can supply all essential amino acids. “Non-essential” means synthesizable, not unimportant.

Protein variety depends on amino-acid type, number and order.

$P=A^n$

$P$ counts sequences, $A$ amino-acid types and $n$ chain length. With 20 coded amino acids, $P=20^n$ and $20^5=3{,}200{,}000$ . Genes specify residue order; the proteome is the set of proteins a cell, tissue or organism expresses. Sequence positions R-groups and creates folding possibilities, although not every sequence is functional.

A folded protein loses its precise shape when heat or extreme pH disrupts stabilizing interactions.

Change	Molecular effect	Consequence
High temperature	weak interactions break	fold and binding surfaces, including active sites, change
Extreme pH	R-group charges change	ionic attractions and H-bonds break

Denaturation changes conformation and function but usually leaves the amino-acid sequence intact. Refolding requires the original interactions to reform before aggregation.

Shared amino-acid groups condense → peptide bonds build a directional backbone → genetic information specifies residue order → positioned R-groups create folding possibilities.

Limiting change	Mechanism	Consequence
Essential amino acid unavailable	a required monomer is missing	synthesis of affected proteins slows
High temperature	stabilizing interactions are disrupted	conformation and function may be lost
pH away from optimum	R-group charges change	ionic attractions and H-bond patterns can be disrupted

R-group property	Possible interaction	Typical consequence in water
Polar, uncharged	Hydrogen bonding	Often compatible with an exposed surface
Acidic or basic	Ionic attraction when oppositely charged	Contacts can change when pH changes charge
Non-polar	Hydrophobic clustering	Often protected from water in a soluble protein
Two cysteines	Covalent disulfide bridge after oxidation	Strong cross-link within or between chains

Hydrophobic clustering is driven by the surrounding water; it is not a conventional bond between non-polar R-groups. These are tendencies rather than fixed locations, because local environment and protein function also matter.

Primary structure is the exact number and order of residues in a polypeptide. DNA is transcribed into mRNA, and translation fixes that order. The sequence therefore decides where each R-group appears and which residues may meet when the chain folds.

Replacing a non-polar residue in a buried core with a charged one can remove a hydrophobic contact and introduce an unfavourable charge.
Replacing cysteine can remove a possible disulfide bridge that held distant parts of the chain together.

A substitution has no automatic outcome. Its effect depends on the new R-group and whether that position contributes to the core, surface, active site or binding interface.

An alpha helix and beta-pleated sheet show repeated hydrogen bonds between backbone groups.

Pattern	Arrangement	Stabilizing basis
α-helix	one segment coils	repeated backbone C=O···H–N bonds
β-sheet	strands align	repeated H-bonds between backbone segments

Secondary structure is local backbone geometry; R-groups project away. These motifs can combine into domains such as coiled coils or β-sandwiches. The complete 3D shape of one chain is tertiary structure.

Tertiary structure is the unique overall three-dimensional fold of one polypeptide. Folding brings residues that may be far apart in the primary sequence close together, allowing their R-groups to stabilize the same compact shape.

One folded polypeptide shows a hydrogen bond, an ionic attraction between charged R-groups, a cysteine disulfide bridge and non-polar R-groups clustered in a hydrophobic interior.

Polar R-groups can form hydrogen bonds.
Oppositely charged R-groups can form ionic attractions that are sensitive to pH.
Two cysteines can form a strong covalent disulfide bridge.
Non-polar R-groups tend to cluster away from water through the hydrophobic effect.

Many weak interactions cooperate across the folded chain, while disulfide bridges provide stronger cross-links. Peptide bonds still belong to the primary backbone; they are not the interactions that define tertiary folding.

A soluble globular protein and a membrane protein compare where polar, charged and non-polar residues face water, lipid tails and an aqueous channel.

Soluble globular protein: non-polar residues commonly cluster in a protected core; polar or charged residues can face water.
Integral membrane surface: non-polar residues can face phospholipid tails.
Water-filled channel: polar or charged residues can line the pore while a non-polar exterior contacts lipid tails.

There is no universal rule that polar residues are always “outside” and non-polar residues are always “inside.” Ask: inside or outside relative to which chemical environment?

Quaternary structure arranges two or more polypeptide chains. A conjugated protein also contains a required non-protein prosthetic group.

The figure shows the quaternary structure of human insulin.

Protein	Assembly	Extra group?
Insulin	A + B chains	none
Collagen	three-chain helix	none
Haemoglobin	2α + 2β	four Fe-containing haem groups

Count chains for quaternary structure; check separately for a prosthetic group.

Feature	Insulin: globular signal	Collagen: fibrous tensile cable
Overall form	Compact two-chain molecule	Long triple helix assembled into fibrils
Solubility	Soluble enough for transport in blood	Insoluble structural material
Sequence and interactions	Three disulfide bridges stabilize a precise receptor-binding surface	Glycine every third residue fits the helix centre; H-bonds and covalent cross-links stabilize fibres
Functional consequence	Reaches target cells and binds its receptor specifically	Staggered molecules and cross-links resist stretching

Globular and fibrous are useful categories only when connected to mechanism. Shape, solubility, residue sequence, molecular interactions and biological role together explain why insulin can signal while collagen can bear tension.

In collagen, triple helices lie parallel in a staggered arrangement, so weak points do not line up; covalent cross-links between neighbouring molecules add tensile strength.

Primary: residue order positions R-groups.
Secondary: backbone hydrogen bonds make local helices and sheets.
Tertiary: distant R-groups stabilize one chain’s complete fold.
Quaternary, when present: several folded chains assemble; conjugated proteins also require a non-protein group.

Sequence → positioned chemistry → local patterns → distant contacts → possible subunit assembly → functional shape and surface. A substitution changes one R-group, pH changes some charges; the effect depends on where the affected interaction sits.

3 marks

The molecules of all amino acids include an amine group, a carboxyl group and an R-group. Draw a diagram to show the structure of an amino acid molecule.

4 marks

Draw molecular diagrams to show the condensation reaction between two amino acids to form a dipeptide.

2 marks

Some of the twenty amino acids that are linked together to make polypeptides in human cells are essential in the diet and others are not. Distinguish between essential and non-essential amino acids.

7 marks

Cells produce a large variety of proteins with different sequences of amino acids. Explain how this is done.

4 marks

Outline the process of protein denaturation.

2 marks

Discuss briefly whether amino acids on the surface of the protein are likely to be polar or non-polar.

1 mark

Hemoglobin is a protein made up of two alpha and two beta polypeptide chains. In sickle cell anemia, a mutation causes one glutamic acid in each beta chain to be replaced by valine, as shown in the image.

Normal beta chain

Sickle beta chain

How does this mutation in hemoglobin cause sickle cell anemia?

3 marks

Explain the secondary structure of this protein molecule.

2 marks

The R-groups of amino acids are very diverse chemically. Interaction between R-groups in different parts of a polypeptide helps to determine the tertiary structure of a protein. List two types of interaction between R-groups.

3 marks

C3. Explain the significance of polar and non-polar amino acids in proteins.

1 mark

This diagram shows the amino acids present in a molecule of insulin, using three-letter abbreviations.

What describes the structure of insulin?

3 marks

Distinguish between fibrous proteins and globular proteins.

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—B2.1 Membranes and membrane transportRead

B1.2 Proteins

Learning objectives

A shared amino-acid framework, variable R-groups

Condensation forms peptide bonds

The scarcest amino acid limits protein synthesis

Sequence order creates enormous protein diversity

Heat and pH can denature a protein

Checkpoint: build a protein, then identify what can limit it

R-group chemistry creates a toolkit of interactions

Primary structure positions folding chemistry

Backbone H-bonds make helices and sheets

Tertiary structure brings distant residues together

A residue's surroundings help determine where it can sit

Quaternary structure and conjugated proteins

Insulin and collagen show how form supports function

Summary: trace protein sequence to function

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