Amino Acids and Proteins - Khan Academy Articles

Amylase, lipase, pepsin

• Digestive enzyme

• breaks down nutrients in food into small pieces that can be readily absorbed

Hemoglobin

• transport

• carry substances throughout the body in blood or lymph

Actin, tubulin, keratin

• structure

• build different structures, like the cytoskeleton

Insulin, glucagon

• hormone signaling

• coordinate the activity of different body systems

Antibodies

• defense

• protect the body from foreign pathogens

Myosin

• contraction

• carry out muscle contraction

Legume storage proteins, egg white (albumin)

• storage

• provide food for the early development of the embryo or the seedling

Essential amino acids - cannot be synthesized by human body; must be obtained from diet

histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine

Non-essential amino acids - can be synthesized by the body

alanine, asparagine, aspartic acid, glutamic acid, serine, arginine, cysteine, glutamine, glycine, proline, and tyrosine

Phosphorylation

Addition of phosphate groups (usually to serine, threonine, or tyrosine), playing a critical role in signaling pathways

Glycosylation

Attachment of carbohydrate groups, affecting protein folding, stability, and cell recognition

Acetylation and Methylation

Modifications that typically occur on lysine residues, influencing gene expression and protein function

Ubiquitination

Attachment of ubiquitin to lysine residues, tagging proteins for degradation

Albumin

• found in egg whites

• 3D shape

• frying an egg is protein denaturation

Primary structure

sequence of amino acids in a polypeptide chain

Sickle cell anemia

The glutamic acid that is normally the sixth amino acid of the hemoglobin β chain (one of two types of protein chains that make up hemoglobin) is replaced by a valine

• the glutamic acid-to-valine amino acid change makes the hemoglobin molecules assemble into long fibers. The fibers distort disc-shaped red blood cells into crescent shapes

Secondary structure

local folded structures that form within a polypeptide due to interactions between atoms of the backbone

• does not involve R groups

• most common types: alpa helix and beta pleated sheet

  • both structures are held in shape by hydrogen bonds, which form between the carbonyl O of one amino acid and the amino H of another

alpha helix - secondary structure

the carbonyl (C=O) of one amino acid is hydrogen bonded to the amino H (N-H) of an amino acid that is four down the chain. (E.g., the carbonyl of amino acid 1 would form a hydrogen bond to the N-H of amino acid 5)

• curled ribbon pattern

• each turn of helix containing 3.6 amino acids

• R groups of amino acids stick outwards so free to interact

Beta pleated sheet - secondary structure

two or more segments of a polypeptide chain line up next to each other, forming a sheet-like structure held together by hydrogen bonds. The hydrogen bonds form between carbonyl and amino groups of backbone, while the R groups extend above and below the plane of the sheet

• strands may be parallel (N and C termini match up)

• or may be antiparallel (N and C termi are positioned next to each other)

Proline

• not compatible with helix

• typically found in bends, unstructured regions between secondary structures

tryptophan, tyrosine, phenylalanine

• have large ring structures in their R groups, so found in B pleated sheets bc they provide plenty of space for side chains

Tertiary Structure

• overall 3D structure

• structure is primarily due to interactions between the R groups of the amino acids that make up the protein

• forces that contribute to structure: hydrogen bonding, ionic bonding, dipole-dipole interactions, London dispersion forces, non-covalent

• hydrophobic on the inside

disulfide bonds

• contribute to tertiary structure

• covalent linkages between the sulfur-containing side chains of cysteines

• much stronger than other bonds

• keep parts of the polypeptide firmly attached to one another

Quaternary Structure

• made up of multiple polypeptide chains (subunits)

• same types of interactions as tertiary

  • mostly weak interactions, such as hydrogen bonding and London Dispersion forces

Denaturation

• when a protein loses its higher-order structure, but not its primary sequence

• usually non-functional

• for some proteins, this can be reversed if the protein is returned to its normal environment

• other times, it is permanent

Chaperon proteins

• assist proteins in folding

Protein folding

1. Hydrophobic effect: non-polar amino acids cluster together to avoid water. Release water molecules into surrounding environment and increasing the system’s entropy

2. Hydrogen bonds: form between side chains to stabilize structure

3. Ionic bonds (salt bridges) act as attractions between positively and negatively charged side chains

4. disulfide bonds: extra reinforcement - strong covalent links

5. van der Waals: help fine-tine and stabilize overall shape

Hydrophobic interactions

Non-polar amino acid side chains tend to cluster together inside the protein, away from the aqueous environment

• major force in stabilizing protein’s structure

• driving force is entropy: as hydrophobic residues aggregate, water molecules are released from their structured arrangements around these residues, increasing the entropy of the system

Hydrogen bonds

• form between polar side chains

• contribute significantly to the protein’s stability

• can occur between side chains and backbone or between side chains themselves

Ionic bonds (salt bridges)

• form between positively charged (basic) and negatively charged (asidic) side chains

• strong and contribute to overall stability of protein structure

Disulfide bonds

• covalent bonds that form between the sulfur atoms and two cysteine residues

• provide significant stabilization, particularly in extracellular proteins

Van der Waals forces

• weak interactions that occur between all atoms that are in close proximity

• help fine-tune protein structure and stability

Entropic contributions to folding

conformational entropy and solvent entropy

Conformational entropy

as a protein folds, it adopts a more ordered structure, which decreases its conformational entropy

• loss is offset by other entropic gains

Solvent entropy

• hydrophobic effect plays a critical role

• hydrophobic molecules clustering releases water molecules into bulk solvent, which increases entropy in surroundings - driving force for folding process

Molecular chaperones

• bind to nascent or partially folded polypeptides, preventing improper interactions that can lead to aggregation or misfolding

• - ex. HSP70

Chaperonins

• are large, cylindrical complexes that provide a protected environment for protein folding

• ex. GroEL/GroES —> GroEL is a barrel-shaped protein that encapsulates the polypeptide, while the GroES acts as a cap

• this isolation prevents aggregation and allows the protein to fold properly within the chamber

• after folding, the protein is released, and the chaperonin complex is ready to assist with another substrate

Denaturation

process that alters a protein’s native conformation, typically due to changes in environmental conditions such as temperature, pH, of chemical exposure

• affects secondary, tertiary, or quaternary structure, but not its primary sequence

Temperature

• elevated temperatures increase the kinetic energy of molecules, disrupting the non-covalent interactions that maintain the protein’s structure

• ex. heat can cause the unfolding of proteins, exposing hydrophobic residues

pH changes

• variations in pH can alter the charge states of amino acid side chains, particularly those with acidic or basic groups

• these changes can disrupt the ionic bonds and hydrogen bonds that are critical for maintaining the protein’s structure

• ex. extreme pH conditions in the stomach denature dietary proteins, aiding in digestion

Chemical agents

• certain chemicals, such as urea and guanidine hydrochloride, can disrupt hydrogen bonding and hydrophobic interactions, leading to protein denaturation

Reversible denaturation

occurs when the protein can refold into its native structure upon the removal of the denaturing agent, allowing it to regain its functionality

Irreversible denaturation

results in a permanent loss of protein structure and function, often due to covalent modifications or aggregation of denatured proteins