B1.2 Proteins

Every amino acid has an alpha carbon bonded to four groups: an amine group, a carboxyl group, a hydrogen atom and a variable R-group.

The amine and carboxyl groups provide the shared chemistry for peptide-bond formation. The R-group varies among amino acids and changes charge, polarity, size and reactivity, thereby influencing protein folding and function.

In two amino-acid diagrams, the backbone groups can be identical while one R-group is non-polar and another charged; both form peptide bonds but interact differently after joining a chain.

The hydrogen on the alpha carbon is part of the generalized structure, and R is not an optional label: it represents the side chain that distinguishes amino acids.

A peptide bond forms when the carboxyl group of one amino acid condenses with the amine group of another, releasing water and creating a covalent C–N link.

OH is removed from the carboxyl group and H from the amine group. Repeating condensation extends the polypeptide from its amino (N) terminus toward its carboxyl (C) terminus.

Two amino acids produce one peptide bond and one water molecule; adding a third amino acid produces a tripeptide with two peptide bonds and releases a second water molecule.

A peptide bond is the covalent link in the backbone, not a hydrogen bond. Hydrogen bonds stabilize later folding levels.

Essential amino acids cannot be synthesized in sufficient amounts and must be obtained from food; non-essential amino acids can be synthesized from other molecules in the body.

Protein synthesis requires every amino acid specified by the sequence. If one essential amino acid is unavailable, translation of that protein is limited even if all other amino acids are abundant.

A well-planned vegan diet can supply all essential amino acids by including sufficient amounts and a suitable variety of plant proteins. The syllabus does not require memorizing lists of essential amino acids.

If a diet supplies too little of one essential amino acid, that amino acid becomes limiting for synthesis of proteins that require it; consuming more of the other amino acids does not remove the limit.

Non-essential means synthesizable, not biologically unimportant. 'Essential' describes dietary supply, not whether the amino acid has a special position in every protein.

The genetic code specifies 20 common amino acids, and peptide chains can contain from a few to thousands of residues in any order, creating an immense variety of possible sequences.

At each position there can be many amino-acid choices, so the number of possible sequences grows exponentially with chain length. Genes specify particular orders; different cells express different sets of proteins, forming their proteomes.

Protein variety depends on amino-acid type, number and order. Sequence positions place different R-group chemistries together during folding, helping determine the final three-dimensional form and function.

Two chains with the same numbers of alanine and glycine can have different primary structures—and potentially different folds—when those residues occur in different orders.

A possible sequence is not automatically a stable functional protein, and a sequence change matters only through its effect on folding, stability, interactions or a functional site.

Protein shape is maintained by weak interactions that can be disrupted by extreme pH or temperature, causing denaturation and loss of function.

Heating increases molecular motion and extreme pH changes charges on R-groups. These changes disturb hydrogen bonds, ionic attractions and other interactions holding the folded chain in its working shape.

Predict a condition effect by asking:

• which interaction is disturbed
• whether the chain unfolds or changes active-site shape
• whether the change is reversible under the conditions

An enzyme may work faster as temperature rises to its optimum, then lose activity sharply when heating disrupts the shape of its active site.

Denaturation changes conformation, not necessarily the amino-acid sequence. Do not treat every loss of activity as peptide-bond hydrolysis.

Amino-acid R-groups may be non-polar hydrophobic, polar hydrophilic, acidic or basic; their chemistry is the basis of protein form and functional diversity.

Hydrophobic R-groups avoid water, polar groups form hydrogen bonds, and acidic/basic groups can carry negative or positive charge and form ionic interactions. Cysteine R-groups can form covalent disulfide bonds.

A soluble globular protein often buries hydrophobic side chains while exposing charged and polar side chains to the aqueous environment.

R-group charge can change with pH. Categories describe chemical tendencies, not permanent placement or charge under every condition.

Primary structure is the exact amino-acid sequence of a polypeptide, and that sequence constrains every later level of folding.

The order places particular R-groups at particular positions. A substitution can create or remove an interaction, alter a bend or change an active site, so sequence is the starting information for conformation.

Trace a sequence change by checking:

• which residue changed
• what chemistry the new R-group adds or removes
• which later interaction or function could shift

Replacing one non-polar residue with a charged residue in a buried region can destabilize folding because the new charge is poorly suited to the hydrophobic interior.

Primary structure means sequence, not the first stage in time only. It remains part of the molecule even after secondary and tertiary folding occur.

Secondary structure is local folding of the polypeptide backbone into patterns such as alpha helices and beta-pleated sheets, stabilized mainly by backbone hydrogen bonds.

Hydrogen bonds form between backbone C=O and N–H groups at regular positions. Their repeated geometry produces a helix or aligns strands into a sheet without requiring the R-groups to form the main stabilizing bonds.

Recognize secondary structure by checking:

• repeated backbone hydrogen bonds
• local helix or sheet geometry
• R-groups projecting away from the backbone pattern

A stretch of chain can coil into an alpha helix when backbone hydrogen bonds repeat along the segment, even though the amino-acid sequence itself remains unchanged.

Secondary structure is not the whole folded protein. Interactions among distant regions and R-groups belong mainly to tertiary structure.

Tertiary structure is the overall three-dimensional shape of one polypeptide, produced by interactions among its R-groups and with the surrounding water.

Non-polar groups tend to be buried, while charged and polar groups can remain exposed or attract one another. Hydrogen bonds, ionic attractions, disulfide links and hydrophobic interactions stabilize the final fold.

Explain a tertiary interaction by naming:

• the two groups involved
• the type of interaction
• how it changes the chain’s shape or stability

A disulfide link between two cysteine R-groups can hold distant parts of a polypeptide together, making the folded shape more resistant to change.

Tertiary structure is not simply ‘all bonds in the protein’. Peptide bonds define the chain; tertiary interactions fold that chain.

R-group polarity influences protein folding: soluble globular proteins usually bury non-polar residues and expose polar or charged residues, whereas integral membrane proteins expose hydrophobic regions to lipid tails.

In water, clustering hydrophobic groups away from water helps stabilize a globular core. In a bilayer, hydrophobic side chains interact favourably with the membrane's hydrocarbon interior while hydrophilic regions face water or line aqueous channels.

Predict placement from environment: aqueous exterior → polar/charged common; soluble core → non-polar common; membrane-spanning surface → hydrophobic; channel pore or exposed loop → hydrophilic common.

An integral channel can have hydrophobic residues facing phospholipid tails and polar residues facing the water-filled pore, satisfying two environments in the same protein.

'Polar outside, non-polar inside' applies to soluble globular proteins, not universally. Active sites, channels and membrane surfaces create important exceptions.

Quaternary structure is the arrangement of two or more polypeptide chains in one functional protein. A conjugated protein also contains a non-polypeptide component; a non-conjugated protein contains only amino-acid chains.

Subunit contacts stabilize the complete structure and can enable coordinated function. In haemoglobin, the haem prosthetic groups bind oxygen while interactions among globin subunits allow affinity to change cooperatively.

An isolated globin chain is not equivalent to complete haemoglobin: oxygen transport depends on both the haem groups and the assembled four-subunit protein.

A single polypeptide has tertiary but no quaternary structure. 'Conjugated' refers to a required non-polypeptide component, not simply to several chains being joined.

Globular proteins are compact and often soluble, suiting mobile signalling, transport or catalytic roles; fibrous proteins are elongated and usually insoluble, suiting structural support.

A globular fold presents a water-compatible surface and brings precise binding groups together. Repeated fibrous organization distributes force along aligned chains and tissues.

Collagen fibrils resist pulling because many aligned triple helices share the load, whereas insulin's compact surface enables specific receptor recognition.

Shape supports function but does not prove it alone. Use solubility, interactions, location and biological role as well as overall appearance.