Anfinsen's dogma
Anfinsen's dogma (also known as the thermodynamic hypothesis) is a postulate in molecular biology championed by the Nobel Prize Laureate Christian B. Anfinsen. The dogma states that, at least for small globular proteins, the native structure is determined only by the protein's amino acid sequence. This amounts to say that, at the environmental conditions (temperature, solvent concentration and composition, etc.) at which folding occurs, the native structure is a unique, stable and kinetically accessible minimum of the free energy. The three conditions:
- uniqueness
- requires that the sequence does not have any other configuration with a comparable free energy. Hence the free energy minimum must be unchallenged.
- stability
- small changes in the surrounding environment cannot give rise to changes in the minimum configuration. This can be pictured as a free energy surface that looks rather like a funnel (with the native state in the bottom of it) than like a soup plate; the free energy surface around the native state must be rather steep and high, in order to provide stability.
- kinetical accessibility
- means that the path in the free energy surface from the unfolded to the folded state must be reasonably smooth or, in other words, that the folding of the chain must not involve highly complex changes in the shape (like knots or other high order conformations).
How the protein reaches this structure is the subject of the field of protein folding, which has a related dogma called Levinthal's paradox. The Levinthal paradox states that the number of possible conformations available to a given protein is astronomically large, such that even a small protein of 100 residues would require more time than the universe has existed to explore all possible conformations (1026 seconds) and choose the appropriate one, it would also arguably make computational prediction of protein structures under the same basis unfeasible if not impossible.
Also, some proteins need the assistance of another protein called a chaperone protein to fold properly. It has been suggested that this disproves Anfinsen's dogma. However, the chaperones do not appear to affect the final state of the protein; they seem to work primarily by preventing aggregation of several protein molecules before the protein is folded.
[edit] References
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This article includes a list of references, related reading or external links, but its sources remain unclear because it lacks inline citations. Please improve this article by introducing more precise citations. (February 2010) |
- Sela M, White FH Jr, Anfinsen CB (1957). "Reductive cleavage of disulfide bridges in ribonuclease". Science 125 (3250): 691–692. doi:10.1126/science.125.3250.691. PMID 13421663.
- White FH (1961). "Regeneration of native secondary and tertiary structures by air oxidation of reduced ribonuclease". J. Biol. Chem. 236: 1353–1360. PMID 13784818.
- Anfinsen CB, Haber E (1961). "Studies on the reduction and re-formation of protein disulfide bonds". J. Biol. Chem. 236: 1361–1363. PMID 13683523.
- Anfinsen CB, Haber E, Sela M, White FH Jr (1961). "The kinetics of formation of native ribonuclease during oxidation of the reduced polypeptide chain". PNAS 47 (9): 1309–1314. doi:10.1073/pnas.47.9.1309. PMC 223141. PMID 13683522. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=223141.
- Anfinsen CB (1973). "Principles that govern the folding of protein chains". Science 181 (4096): 223–230. doi:10.1126/science.181.4096.223. PMID 4124164.
- Moore S, Stein WH (1973). "Chemical structures of pancreatic ribonuclease and deoxyribonuclease". Science 180 (4085): 458–464. doi:10.1126/science.180.4085.458. PMID 4573392.
