Dogma de Anfinsen

O dogma de Anfinsen (tamén chamado hipótese termodinámica) é un postulado de bioloxía molecular sobre a determinación da estrutura das proteínas, que di que, polo menos para as proteínas globulares pequenas, a estrutura nativa dunha proteína está determinada soamente pola súa secuencia de aminoácidos (estrutura primaria). Este dogma foi defendido polo premio Nobel (ver [1]) Christian B. Anfinsen a partir dos seus traballos sobre o pregamento da ribonucclease A. The postulate amounts to saying 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:

Estrutura tridinensional da ribonuclease A pregada.

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 more like a funnel (with the native state in the bottom of it) rather than like a soup plate (with several closely related low-energy states); 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.

Prions are an exception to Anfinsen's dogma. Prions are stable conformations of proteins which differ from the native folding state. In Bovine spongiform encephalopathy (Mad Cow Disease), native proteins re-fold into a different stable conformation, which causes fatal amyloid buildup. Other amyloid diseases, including Alzheimer's disease and Parkinson's disease, are also exceptions to Anfinsen's dogma.

Véxase tamén

Outros artigos

• Pregamento das proteínas
• Estrutura das proteínas

Outras lecturas

• Sela M, White FH Jr, Anfinsen CB (1957). "Reductive cleavage of disulfide bridges in ribonuclease". Science 125 (3250): 691–692. PMID 13421663. doi:10.1126/science.125.3250.691. 
• Anfinsen CB, Haber E (1961). "Studies on the reduction and re-formation of protein disulfide bonds". J. Biol. Chem. 236: 1361–1363. PMID 13683523. 
• Moore S, Stein WH (1973). "Chemical structures of pancreatic ribonuclease and deoxyribonuclease". Science 180 (4085): 458–464. PMID 4573392. doi:10.1126/science.180.4085.458.