Hofmeister series
Encyclopedia
The Hofmeister series or lyotropic series is a classification of ion
s in order of their ability to salt out or salt in proteins. The effects of these changes were first worked out by Franz Hofmeister
, who studied the effects of cations and anions on the solubility of protein
s.
Hofmeister discovered a series of salts that have consistent effects on the solubility of proteins and (it was discovered later) on the stability of their secondary
and tertiary structure
. Anions appear to have a larger effect than cations, and are usually ordered
(This is a partial listing; many more salts have been studied.)
The order of cations is usually given as
The mechanism of the Hofmeister series is not entirely clear, but does not seem to result from changes in general water structure, instead more specific interactions between ions and proteins and ions and the water molecules directly contacting the proteins may be more important.
Early members of the series increase solvent surface tension
and decrease the solubility of nonpolar molecules ("salting out
"); in effect, they strengthen the hydrophobic interaction. By contrast, later salts in the series increase the solubility of nonpolar molecules ("salting in
") and decrease the order in water; in effect, they weaken the hydrophobic effect
. The salting out effect is commonly exploited in protein purification
through the use of ammonium sulfate precipitation
.
However, these salts also interact directly with proteins (which are charged and have strong dipole moments) and may even bind specifically (e.g., phosphate and sulfate binding to ribonuclease A
). Ions that have a strong 'salting in' effect such as I- and SCN- are strong denaturants, because they salt in the peptide group, and thus interact much more strongly with the unfolded form of a protein than with its native form. Consequently, they shift the chemical equilibrium
of the unfolding reaction towards unfolded protein.
Ion
An ion is an atom or molecule in which the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge. The name was given by physicist Michael Faraday for the substances that allow a current to pass between electrodes in a...
s in order of their ability to salt out or salt in proteins. The effects of these changes were first worked out by Franz Hofmeister
Franz Hofmeister
Franz Hofmeister was an early protein scientist, and is famous for his studies of salts that influence the solubility and conformational stability of proteins...
, who studied the effects of cations and anions on the solubility of protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s.
Hofmeister discovered a series of salts that have consistent effects on the solubility of proteins and (it was discovered later) on the stability of their secondary
Secondary structure
In biochemistry and structural biology, secondary structure is the general three-dimensional form of local segments of biopolymers such as proteins and nucleic acids...
and tertiary structure
Tertiary structure
In biochemistry and molecular biology, the tertiary structure of a protein or any other macromolecule is its three-dimensional structure, as defined by the atomic coordinates.-Relationship to primary structure:...
. Anions appear to have a larger effect than cations, and are usually ordered
(This is a partial listing; many more salts have been studied.)
The order of cations is usually given as
The mechanism of the Hofmeister series is not entirely clear, but does not seem to result from changes in general water structure, instead more specific interactions between ions and proteins and ions and the water molecules directly contacting the proteins may be more important.
Early members of the series increase solvent surface tension
Surface tension
Surface tension is a property of the surface of a liquid that allows it to resist an external force. It is revealed, for example, in floating of some objects on the surface of water, even though they are denser than water, and in the ability of some insects to run on the water surface...
and decrease the solubility of nonpolar molecules ("salting out
Salting out
Salting out is a method of separating proteins based on the principle that proteins are less soluble at high salt concentrations. The salt concentration needed for the protein to precipitate out of the solution differs from protein to protein...
"); in effect, they strengthen the hydrophobic interaction. By contrast, later salts in the series increase the solubility of nonpolar molecules ("salting in
Salting in
Salting in refers to the effect where increasing the ionic strength of a solution increases the solubility of some solute . This effect tends to be observed at lower ionic strengths....
") and decrease the order in water; in effect, they weaken the hydrophobic effect
Hydrophobic effect
The hydrophobic effect is the observed tendency of nonpolar substances to aggregate in aqueous solution and exclude water molecules. The name, literally meaning "water-fearing," describes the segregation and apparent repulsion between water and nonpolar substances...
. The salting out effect is commonly exploited in protein purification
Protein purification
Protein purification is a series of processes intended to isolate a single type of protein from a complex mixture. Protein purification is vital for the characterization of the function, structure and interactions of the protein of interest. The starting material is usually a biological tissue or...
through the use of ammonium sulfate precipitation
Ammonium sulfate precipitation
Ammonium sulfate precipitation is a method used to purify proteins by altering their solubility. It is a specific case of a more general technique known as salting out....
.
However, these salts also interact directly with proteins (which are charged and have strong dipole moments) and may even bind specifically (e.g., phosphate and sulfate binding to ribonuclease A
Ribonuclease A
Ribonuclease A is a pancreatic ribonuclease that cleaves single-stranded RNA. Bovine pancreatic RNase A is one of the classic model systems of protein science.-History:...
). Ions that have a strong 'salting in' effect such as I- and SCN- are strong denaturants, because they salt in the peptide group, and thus interact much more strongly with the unfolded form of a protein than with its native form. Consequently, they shift the chemical equilibrium
Chemical equilibrium
In a chemical reaction, chemical equilibrium is the state in which the concentrations of the reactants and products have not yet changed with time. It occurs only in reversible reactions, and not in irreversible reactions. Usually, this state results when the forward reaction proceeds at the same...
of the unfolding reaction towards unfolded protein.