Protein folding

Protein folding is the process of their proteins obtained by the three-dimensional structure. It takes place during and after the synthesis of the peptide chain and is a prerequisite for the correct function of the protein. Is caused by the folding of the tiniest movement of the solvent molecules (water molecules) and by electrical attraction forces within the protein molecule. Some proteins can achieve proper folding using only certain enzymes or chaperone proteins.

Protein synthesis

Proteins are synthesized on ribosomes as linear polypeptide chains of amino acids. The sequence of the individual amino acids forming the primary structure of the protein. During or after the synthesis of the polypeptide chain folds into a defined three-dimensional structure ( tertiary structure ), the structure of smaller elements ( secondary structure ) is constructed. Some proteins consist of more than one polypeptide chain. Forms such an oligomer of several polypeptide chains in tertiary structure, then one speaks of a quaternary structure.

The amino acid chain increases during folding in a split second to the native conformations, ie the biologically functional conformation. This process is called Levinthal paradox. The finished folded protein usually has the lowest possible Gibbs free energy ( Anfinsen dogma ). The exact process of protein folding is still unclear and is a current subject of research in biochemistry dar. For some proteins, the folding proceeds through an intermediate state, the molten globule is called. It comes to an aggregation of the hydrophobic amino acid residues, where within a few milliseconds all the secondary structure elements are formed. Only then is the formation of the tertiary structure, which may take several seconds to complete.

Structure and Function

See the main article: Protein structure

The specific function of a protein can only be defined by its structure. Misfolded proteins are usually detected in the protein quality control and degraded in the proteasome. Should this reduction fails, it comes to protein accumulation, which can cause various diseases depending on the protein. These diseases are known as protein folding diseases and can be broken down as follows:

• Those in which mutations preventing the correct folding, whereby the protein no longer functions. Examples: forms of cancer are due to mutations in the p53 protein.
• Those in which mutations preventing the correct folding, whereby the aggregated protein. Examples: sickle cell anemia, aggregated in the hemoglobin; Alzheimer's disease; Parkinson 's disease; Huntington's disease.
• Those in which mutations preventing the correct folding, whereby the protein is toxic. Example: BSE caused by prions.

Denaturation

See the main article: Denaturation (biochemistry )

When folding the protein adopts the native ( structured or biologically functional ) state. The reverse process is called denaturation. Folding and denaturation of proteins similar to phase transitions of the first order, ie extensive quantities such as volume and thermal energy change by leaps and bounds. The denaturation of proteins is triggered for example by heat, extreme pH conditions or extreme salt concentrations.

1972 Christian B. Anfinsen was awarded the Nobel Prize in Chemistry for the observation that small proteins after denaturation can fold into the native form as soon as they are exposed to ambient conditions in which it is stable. Anfinsen concluded from this observation that the native structure of each protein is determined by its amino acid sequence. An exception is rare metamorphic proteins such as lymphotactin, which have two fundamentally different secondary structures.

Research

The first comprehensive theory of protein folding was developed in the 1920s by the Chinese scientists Hsien Wu. In the European / American space, the first significant work of Christian B. Anfinsen (Nobel Prize in Chemistry (1972 ) ) were carried out in the 1950s.

At present the project " Folding @ home" Stanford University races to simulate these folds, can help with the internet users by providing computing power. The projects " POEM @ home" at the University of Karlsruhe and " Rosetta @ home" the University of Washington to pursue this goal. All three projects use different approaches for simulating protein folding. Another approach adopted by the computer game Foldit, in which players try to fold a protein cleverly as possible, and to take it as a low energy level.

In addition, every two years the community experiment CASP instead, which research groups provides the opportunity to test the quality of their methods for prediction of protein structures starting from the primary structure and to gain an overview of the current status of this field of research.