His-Tag Protein Purification is a series of processes intended to isolate target protein from a complex mixture. A His-Tag is an amino acid motif in proteins that typically consists of at least six histidine (His) residues, often at the N- or C-terminus of the protein. Several metal cations have high affinities for imidazole, the function group of His-Tag. Transition metal imidazole complexes are well known for M2+ (M = Mn, Fe, Co, Ni, Cu). Nickel is a widely used metal ion in the purification of His-Tag protein.
Fig.1 Schematic diagram of His-Tag protein purification principle.
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Add His-Tag
The addition of polyhistidine affinity tags to proteins can be accomplished in several ways. They are small in size, low in charge, and easily integrated into target genes by PCR or site-directed mutagenesis. -
Binding
A crude solution containing the His-Tag protein is applied to the column and binds based on the affinity tag-matrix interaction. -
Washing
Other proteins are washed away with the appropriate wash buffer. These buffers should already contain low molar amounts of imidazole. -
Elution
Specifically bound protein is eluted from the column, usually by competitive binding of similar molecules, by protease cleavage of the tag, or by destabilization of affinity tag-substrate interactions, for example by changing pH. The pure eluate can then be collected in reaction tubes for further study.
- His-Tag is very small and does not affect the downstream application of the protein.
- The His-Tag at the N-terminal is compatible with the bacterial transcription and translation mechanism, which is beneficial to protein expression.
- The use of IMAC (Immobilized Metal Ion Affinity Chromatography) to purify the His-Tag fusion protein is more convenient [1].
- His-Tag has little effect on the properties of the target protein and will not form dimers.
- The immunogenicity of His-Tag is relatively low, and the purified protein can be directly injected into animals for immunization and antibody preparation.
- It can be combined with other affinity tags to form dual affinity tags, which can be applied to various expression systems.
- Target proteins with strong hydrophobicity can be purified in the presence of non-ionic surfactant.
- Inclusion body proteins can be purified under denaturing conditions.
- Affinity tags like His6 or GST paired with an immobilized ligand (e.g. Ni2+ agarose resin) can be used to specifically bind to a target protein complex in order to purify and identify it.
- Semi-quantitation with known His-Tag protein as standards.
Thermal Cyclers
PCR Workstation / PCR Hood
PCR Consumables
Laboratory Rockers and Shakers
Protein Purification Columns
Pipettes and Pipette Tips
Chromatography Fraction Collector
STEMart provides you with a variety of His-Tag protein purification equipment to meet your various R&D and application needs. If you have any questions or requirements for His-Tag protein purification equipment, please feel free to contact us.
Reference
- Spriestersbach A, Kubicek J, Schäfer F, Block H, Maertens B. Purification of His-Tagged Proteins. Methods Enzymol. 2015; 559: 1-15. Doi: 10.1016/bs.mie.2014.11.003. Epub 2015 May 4. PMID: 26096499