Protein Structure

Proteins have four levels of structural organization, each building upon the last to create functional molecular machines.

The Hierarchy of Protein Structure

A protein's structure is organized into four hierarchical levels. Each level is essential for the protein to perform its biological function. The sequence of amino acids (primary structure) determines how the protein folds through all subsequent levels.

PrimarySecondaryTertiaryQuaternary
Level 1

Primary Structure

The primary structure is simply the linear sequence of amino acids in a polypeptide chain. Think of it as the "recipe" for a protein - the specific order of amino acids linked together by peptide bonds.

This sequence is encoded by the gene that codes for the protein. Even a single amino acid change can dramatically alter a protein's function - as seen in diseases like sickle cell anemia, where one amino acid substitution changes the shape of hemoglobin.

Key Points:

  • Determined by the genetic code (DNA)
  • Amino acids linked by peptide bonds
  • Read from N-terminus to C-terminus
  • Dictates all higher structural levels

Amino Acid Chain Example

Met-Ala-Lys-Glu-Phe-Leu-Ser-Arg-...

Each three-letter code represents an amino acid. The sequence determines everything about how the protein will fold and function.

The 20 Standard Amino Acids

Glycine (Gly), Alanine (Ala), Valine (Val), Leucine (Leu), Isoleucine (Ile), Proline (Pro), Phenylalanine (Phe), Tyrosine (Tyr), Tryptophan (Trp), Serine (Ser), Threonine (Thr), Cysteine (Cys), Methionine (Met), Asparagine (Asn), Glutamine (Gln), Aspartic Acid (Asp), Glutamic Acid (Glu), Lysine (Lys), Arginine (Arg), Histidine (His)

Common Secondary Structures

🌀 Alpha Helix (α-helix)

A right-handed coil stabilized by hydrogen bonds between amino acids 4 residues apart. Common in membrane proteins and DNA-binding proteins.

╭─────╮
│     │
╰─────╯
  ↓
╭─────╮
│     │
╰─────╯

📊 Beta Sheet (β-sheet)

Extended strands lying side-by-side, connected by hydrogen bonds. Can be parallel or antiparallel. Found in silk and many enzymes.

→→→→→→→
←←←←←←←
→→→→→→→
Level 2

Secondary Structure

Secondary structure refers to local folding patterns within the polypeptide chain, primarily stabilized by hydrogen bonds between the backbone atoms (not the side chains).

The two main types are alpha helices and beta sheets. These regular, repeating patterns form spontaneously based on the amino acid sequence and provide the basic framework for protein architecture.

Key Points:

  • Stabilized by backbone hydrogen bonds
  • Alpha helices: spiral structures (3.6 residues/turn)
  • Beta sheets: extended strands side-by-side
  • Loops and turns connect these elements
Level 3

Tertiary Structure

Tertiary structure is the overall 3D shape of a single polypeptide chain. It results from interactions between the amino acid side chains (R groups), not just the backbone.

This level of structure creates the protein's functional sites - the pockets, grooves, and surfaces that allow it to bind to other molecules and perform its specific function.

Stabilizing Forces:

  • Disulfide bonds: Covalent bonds between cysteine residues
  • Hydrophobic interactions: Nonpolar residues cluster inside
  • Ionic bonds: Between charged amino acids
  • Hydrogen bonds: Between polar side chains

Protein Folding

💧

Hydrophobic Core

Nonpolar amino acids hide from water in the protein's interior

🔗

Disulfide Bridges

Covalent bonds lock distant parts of the chain together

⚡

Salt Bridges

Ionic attractions between oppositely charged residues

Protein Misfolding: When proteins fold incorrectly, they can aggregate and cause diseases like Alzheimer's, Parkinson's, and prion diseases.

Examples of Quaternary Structure

Hemoglobin

A tetramer (4 subunits): 2 alpha chains + 2 beta chains. Each subunit carries one heme group for oxygen binding.

α₁α₂β₁β₂

Collagen

Three polypeptide chains wound together in a triple helix, providing incredible tensile strength.

Chain 1Chain 2Chain 3

ATP Synthase

A molecular machine with multiple subunits that rotates to produce ATP - the energy currency of cells.

F₀ complexF₁ complex
Level 4

Quaternary Structure

Quaternary structure describes how multiple polypeptide chains(subunits) come together to form a functional protein complex. Not all proteins have quaternary structure - only those made of more than one chain.

The subunits can be identical (homomeric) or different (heteromeric). This level of organization allows for cooperativity, regulation, and the creation of large molecular machines.

Key Points:

  • Multiple polypeptide chains working together
  • Same interactions as tertiary structure
  • Allows cooperative binding (e.g., O₂ in hemoglobin)
  • Enables regulation and allosteric control

The Protein Folding Problem

One of the greatest challenges in biology has been predicting how a protein will fold based solely on its amino acid sequence. This is called the protein folding problem.

In 2020, DeepMind's AlphaFold AI system achieved a breakthrough in predicting protein structures with near-experimental accuracy. This has revolutionized structural biology and drug discovery.

Why Structure Matters:

  • Drug design requires knowing the target protein's shape
  • Understanding disease mechanisms
  • Engineering proteins for industrial applications
  • Studying evolution and protein families

Explore Common Proteins

Now that you understand protein structure, learn about specific proteins that are essential for life.

View Common Proteins