Protein folding
Say it: PROH-teen FOHL-ding
Protein folding is the process by which a newly made chain of amino acids coils and folds into the specific three-dimensional shape it needs to work.
Definition
What is protein folding?
Protein folding is the process by which a polypeptide, the chain of amino acids made on a ribosome, takes up its working three-dimensional structure, called its native state. Folding is driven mainly by the hydrophobic effect: nonpolar side chains bury themselves in the core of the protein, away from water, while polar and charged ones stay on the surface. Hydrogen bonds hold local alpha helices and beta sheets in shape, and ionic bonds, van der Waals forces and covalent disulfide bridges stabilize the overall fold.
Around 1960, Christian Anfinsen showed that the enzyme ribonuclease, once unfolded, could refold on its own in a test tube, showing that the amino acid sequence alone carries the information for the native shape. Folding is fast, often taking milliseconds to seconds, because the chain does not test every possible shape but moves downhill on an energy landscape pictured as a funnel. In crowded cells, molecular chaperones such as heat shock proteins help by stopping unfinished chains from clumping together.
Misfolded proteins are normally refolded or destroyed, but some build up as aggregates linked to Alzheimer's disease, Parkinson's disease, amyloidosis and prion diseases. Predicting structure from sequence was a central problem of biology for decades; computer methods that now do this with high accuracy were recognized by the 2024 Nobel Prize in Chemistry.
Word parts
Where does the term “protein folding” come from?
- prote-
- protein, from a word for first or primaryGreek proteios, via protein
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Terms that go with it
- ProteinA protein is a large molecule made of one or more chains of amino acids, folded into a specific shape that determines its job in the body.
- DenaturationIn biochemistry, denaturation is the unfolding of a protein or nucleic acid by heat, acid or chemicals, which ruins its shape but not its sequence.
- Amino acidAn amino acid is a small organic molecule with an amino group, a carboxyl group and a side chain; amino acids link together to form proteins.
- Quaternary structureQuaternary structure is the way two or more folded polypeptide chains, called subunits, fit together to form a single working protein.
- AmyloidosisAmyloidosis is a group of diseases in which misfolded proteins clump into insoluble amyloid fibrils that build up in organs and disrupt how they work.
- Hydrogen bondA hydrogen bond is a weak attraction between a slightly positive hydrogen atom, bonded to oxygen or nitrogen, and a nearby electronegative atom.
Sources
Checked against
Written for biofideX in plain words, after checking these references:
- OpenStax Biology 2e, 3.4 Proteins
- Dill et al. (2008), The Protein Folding Problem, Annual Review of Biophysics
- NCBI MeSH: Protein Folding
- The Nobel Prize in Chemistry 2024: Press release
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