[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Biochemistry](https://durgical.com/en/biochemistry/) › Protein structure and folding

[Biochemistry](https://durgical.com/en/biochemistry/) · Topic

# Protein structure and folding

A protein is a chain of amino acids that folds into a precise shape; if it misfolds, it stops working or piles up and damages tissues.

Updated 2026-11-01

## Key facts

- Primary: the sequence joined by peptide bonds (planar, almost always trans). Secondary: α-helix and β-sheet, held by backbone hydrogen bonds.
- Tertiary: the 3D fold of one chain (hydrophobic core, disulfide bridges, ionic bonds). Quaternary: several chains together, such as haemoglobin α₂β₂.
- Sequence determines the fold (Anfinsen), but in the cell chaperones (HSP70, HSP60 chaperonins) and enzymes such as protein disulfide isomerase help.
- Misfolded proteins are tagged with ubiquitin and destroyed in the proteasome; if they escape, they form aggregates such as amyloid (cross-β fibrils).
- Denaturation (heat, extreme pH, urea, detergents) destroys secondary to quaternary structure but not peptide bonds.

## In detail

- The peptide bond has partial double-bond character: it does not rotate, and the chain bends only at the φ and ψ angles of the α carbon.
- α-helix: 3.6 residues per turn; each residue's C=O hydrogen-bonds to the N–H four residues ahead. Proline interrupts it.
- β-sheet: extended strands side by side (parallel or antiparallel), linked by hydrogen bonds between strands; β-turns often contain glycine and proline.
- In water, hydrophobic side chains hide in the core and polar ones stay on the surface: this is the main driving force of folding.
- Domains are folded units that recur between proteins (for example immunoglobulin-like domains or the EGF-like domains of fibrillin).
- In the endoplasmic reticulum, proteins that fail to fold switch on the unfolded protein response (UPR); if it persists, the cell undergoes apoptosis.
- Conformational diseases: α1-antitrypsin Z polymerises in the hepatocyte; the prion converts the normal protein into its β form; unstable transthyretin forms amyloid.

**Also called**
Levels of protein structure, Chaperones

## Clinical notes

- Amyloidosis, prion diseases, Alzheimer disease (β-amyloid and tau) and Parkinson disease (α-synuclein) share one problem: misfolded proteins that aggregate.
- “Stabiliser” drugs such as tafamidis hold transthyretin in its native shape and slow amyloid formation.
- In cystic fibrosis, the commonest CFTR variant (F508del) misfolds and is degraded before it reaches the membrane.

## Related conditions

- [Amyloidosis](https://durgical.com/en/conditions/amyloidosis/)
- [Prion diseases (Creutzfeldt–Jakob)](https://durgical.com/en/conditions/prion-diseases/)
- [α1-antitrypsin deficiency](https://durgical.com/en/conditions/1-antitrypsin-deficiency/)
- [Alzheimer disease](https://durgical.com/en/conditions/alzheimer-disease/)
- [Sickle cell disease](https://durgical.com/en/conditions/sickle-cell-disease/)
- [Cystinuria](https://durgical.com/en/conditions/cystinuria/)

## Related

- [Amino acids: structure, charge and pKa](https://durgical.com/en/biochemistry/topics/amino-acids-structure-charge-and-pka/)
- [Collagen](https://durgical.com/en/biochemistry/enzymes/collagen/)
- [Prion protein (PrP)](https://durgical.com/en/biochemistry/enzymes/prion-protein/)
- [Transthyretin (prealbumin)](https://durgical.com/en/biochemistry/enzymes/transthyretin/)
- [α1-antitrypsin](https://durgical.com/en/biochemistry/enzymes/1-antitrypsin/)
- [Hemoglobin and 2,3-BPG](https://durgical.com/en/biochemistry/enzymes/hemoglobin-and-2-3-bpg/)
- [Myoglobin](https://durgical.com/en/biochemistry/enzymes/myoglobin/)
- [Immunoglobulins (antibodies)](https://durgical.com/en/biochemistry/enzymes/immunoglobulins/)

## Test yourself

Think of the answer, then tap the question to see it.

## What kind of bond holds the α-helix and the β-sheet together?

Hydrogen bonds between the C=O and N–H groups of the peptide backbone, not between side chains.

## Which levels of structure are lost when a protein is denatured by heat?

Secondary, tertiary and quaternary; the peptide bonds (primary structure) stay intact.

## Which amino acid interrupts an α-helix, and why?

Proline: its amino group sits in a ring, so it has no N–H for the hydrogen bond, and its rigid angle does not fit the helix.

## What structure do all amyloid fibrils share?

The cross-β sheet: β-strands running perpendicular to the fibril axis; that is why they stain with Congo red.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/biochemistry/topics/protein-structure-and-folding/)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [What are proteins and what do they do?: MedlinePlus Genetics](https://medlineplus.gov/genetics/understanding/howgeneswork/protein/) (MedlinePlus, US National Library of Medicine, 2026); [PDB-101: Molecule of the Month: Myoglobin](https://pdb101.rcsb.org/motm/1) (RCSB Protein Data Bank (PDB-101), 2026); [Amyloid fiber formation](https://reactome.org/PathwayBrowser/#/R-HSA-977225) (Reactome, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

[← All of biochemistry](https://durgical.com/en/biochemistry/)

## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake

Representative model, for educational purposes only.

---
Source: https://durgical.com/en/biochemistry/topics/protein-structure-and-folding/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/topics/protein-structure-and-folding/