Tetrameric protein

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(Redirected from
Tetramer protein
)
For other uses, see Tetramer.
two protein subunits bind to form a dimer. Two dimers then bind to form the final tetramer.
The formation of the sorbitol dehydrogenase tetramer from its monomers via dimers.

A tetrameric protein is a

heterodimer subunits (such as hemoglobin
).

Subunit interactions in tetramers

The interactions between subunits forming a tetramer is primarily determined by non

electrostatic interactions are the primary sources for this binding process between subunits. For homotetrameric proteins such as sorbitol dehydrogenase (SDH), the structure is believed to have evolved going from a monomeric to a dimeric and finally a tetrameric structure in evolution. The binding process in SDH and many other tetrameric enzymes can be described by the gain in free energy which can be determined from the rate of association and dissociation.[1]
The above image shows the assembly of the four subunits (A,B,C and D) in SDH.

Hydrogen bonds between subunits

Hydrogen bonding networks between subunits has been shown to be important for the stability of the tetrameric quaternary protein structure. For example, a study of SDH which used diverse methods such as protein sequence alignments, structural comparisons, energy calculations, gel filtration experiments and enzyme kinetics experiments, could reveal an important hydrogen bonding network which stabilizes the tetrameric quaternary structure in mammalian SDH.[1]

Tetramers in immunology

In

Sendai virus specific cytotoxic T cell in a C57BL/6
mouse. Antigen specific responses can be measured as CD8+, tetramer+ T cells as a fraction of all CD8+ lymphocytes.

The reason for using a tetramer, as opposed to a single labeled MHC class I molecule is that the tetrahedral tetramers can bind to three

TCRs
at once, allowing specific binding in spite of the low (1 micromolar) affinity of the typical class I-peptide-TCR interaction. MHC class II tetramers can also be made, although these are more difficult to work with practically.[2]

Homotetramers and heterotetramers

glycosidase). Each subunit has the same amino acid
sequence.
haemoglobin
, made up of four subunits of two different types (coloured red and blue.)

A homotetramer is a protein complex made up of four identical subunits which are associated but not covalently bound.[3] Conversely, a heterotetramer is a 4-subunit complex where one or more subunits differ.[4]

Examples of homotetramers include:

Examples of heterotetramers include haemoglobin (pictured), the NMDA receptor, some aquaporins,[7] some AMPA receptors, as well as some enzymes.[8]

Purification of heterotetramers

Ion-exchange chromatography is useful for isolating specific heterotetrameric protein assemblies, allowing purification of specific complexes according to both the number and the position of charged peptide tags.[9][10] Nickel affinity chromatography may also be employed for heterotetramer purification.[11]

Intragenic complementation

Multiple copies of a polypeptide encoded by a gene often can form an aggregate referred to as a multimer. When a multimer is formed from polypeptides produced by two different mutant alleles of a particular gene, the mixed multimer may exhibit greater functional activity than the unmixed multimers formed by each of the mutants alone. When a mixed multimer displays increased functionality relative to the unmixed multimers, the phenomenon is referred to as intragenic complementation. In humans, argininosuccinate lyase (ASL) is a homotetrameric enzyme that can undergo intragenic complementation. An ASL disorder in humans can arise from mutations in the ASL gene, particularly mutations that affect the active site of the tetrameric enzyme. ASL disorder is associated with considerable clinical and genetic heterogeneity which is considered to reflect the extensive intragenic complementation occurring among different individual patients.[12][13][14]

References

  1. ^
    S2CID 22090973
    .
  2. PMID 26076649
    .
  3. ^ "GO term: protein homotetramerization". YeastGenome. Archived from the original on 27 September 2011. Retrieved 14 May 2011.
  4. ^ "GO term: protein heterotetramerization". YeastGenome. Archived from the original on 27 September 2011. Retrieved 14 May 2011.
  5. PMID 2649892
    .
  6. PMID 15231793
    .
  7. PMID 10460172
    .
  8. PMID 20139160
    .
  9. PMID 10875936
    .
  10. PMID 24056174
    .
  11. PMID 16554831
    .
  12. PMID 9256435
    .
  13. S2CID 1254964
    .
  14. PMID 11747433
    .

External links
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