Dimerization

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In chemistry, dimerization is the process of joining two identical or similar molecular entities by bonds. The resulting bonds can be either strong or weak. Many symmetrical chemical species are described as dimers, even when the monomer is unknown or highly unstable. [1]

Contents

The term homodimer is used when the two subunits are identical (e.g. A–A) and heterodimer when they are not (e.g. A–B). The reverse of dimerization is often called dissociation. When two oppositely-charged ions associate into dimers, they are referred to as Bjerrum pairs, [2] after Danish chemist Niels Bjerrum.

Noncovalent dimers

Dimers of carboxylic acids are often found in the vapour phase. Carboxylic acid dimers.png
Dimers of carboxylic acids are often found in the vapour phase.

Anhydrous carboxylic acids form dimers by hydrogen bonding of the acidic hydrogen and the carbonyl oxygen. For example, acetic acid forms a dimer in the gas phase, where the monomer units are held together by hydrogen bonds. [3] Many OH-containing molecules form dimers, e.g. the water dimer.

Excimers and exciplexes are excited structures with a short lifetime. For example, noble gases do not form stable dimers, but they do form the excimers Ar2*, Kr2* and Xe2* under high pressure and electrical stimulation. [4]

Covalent dimers

The dimerization of cyclopentadiene gives dicyclopentadiene, although this might not be readily apparent on initial inspection. This dimerization is reversible Dicyclopentadiene structure.svg
The dimerization of cyclopentadiene gives dicyclopentadiene, although this might not be readily apparent on initial inspection. This dimerization is reversible

Molecular dimers are often formed by the reaction of two identical compounds e.g.: 2A → A−A. In this example, monomer "A" is said to dimerize to give the dimer "A−A".

Dicyclopentadiene is an asymmetrical dimer of two cyclopentadiene molecules that have reacted in a Diels-Alder reaction to give the product. Upon heating, it "cracks" (undergoes a retro-Diels-Alder reaction) to give identical monomers:

Many nonmetallic elements occur as dimers: hydrogen, nitrogen, oxygen, and the halogens fluorine, chlorine, bromine and iodine. Some metals form a proportion of dimers in their vapour phase: dilithium (Li2), disodium (Na2), dipotassium (K2), dirubidium (Rb2) and dicaesium (Cs2). Such elemental dimers are homonuclear diatomic molecules.

Polymer chemistry

In the context of polymers, "dimer" also refers to the degree of polymerization 2, regardless of the stoichiometry or condensation reactions.

One case where this is applicable is with disaccharides. For example, cellobiose is a dimer of glucose, even though the formation reaction produces water:

Here, the resulting dimer has a stoichiometry different from the initial pair of monomers.

Disaccharides need not be composed of the same monosaccharides to be considered dimers. An example is sucrose, a dimer of fructose and glucose, which follows the same reaction equation as presented above.

Amino acids can also form dimers, which are called dipeptides. An example is glycylglycine, consisting of two glycine molecules joined by a peptide bond. Other examples include aspartame and carnosine.

Inorganic and organometallic dimers

Many molecules and ions are described as dimers, even when the monomer is elusive.

Boranes

Borane and diborane Borane & Diborane.jpg
Borane and diborane

Diborane (B2H6) is an dimer of borane, which is elusive and rarely observed. Almost all compounds of the type R2BH exist as dimers. [5]

Organoaluminium compounds

Trimethylaluminium dimer Trimethylaluminium dimer.png
Trimethylaluminium dimer

Trialkylaluminium compounds can exist as either monomers or dimers, depending on the steric bulk of the groups attached. For example, trimethylaluminium exists as a dimer, but trimesitylaluminium adopts a monomeric structure. [6]

Organochromium compounds

Cyclopentadienylchromium tricarbonyl dimer exists in measureable equilibrium quantities with the monometallic radical (C5H5)Cr(CO)3. [7]

Biochemical dimers

Pyrimidine dimers

Pyrimidine dimers (also known as thymine dimers) are formed by a photochemical reaction from pyrimidine DNA bases when exposed to ultraviolet light. [6] This cross-linking causes DNA mutations, which can be carcinogenic, causing skin cancers. [6] When pyrimidine dimers are present, they can block polymerases, decreasing DNA functionality until it is repaired. [6]

Protein dimers

Tubulin dimer Tubulin dimer.png
Tubulin dimer

Protein dimers arise from the interaction between two proteins which can interact further to form larger and more complex oligomers. [8] For example, tubulin is formed by the dimerization of α-tubulin and β-tubulin and this dimer can then polymerize further to make microtubules. [9] For symmetric proteins, the larger protein complex can be broken down into smaller identical protein subunits, which then dimerize to decrease the genetic code required to make the functional protein. [8]

G protein-coupled receptors

As the largest and most diverse family of receptors within the human genome, G protein-coupled receptors (GPCR) have been studied extensively, with recent studies supporting their ability to form dimers. [10] GPCR dimers include both homodimers and heterodimers formed from related members of the GPCR family. [11] While not all, some GPCRs require dimerization to function, such as GABAB-receptor, emphasizing the importance of dimers in biological systems. [12]

Receptor tyrosine kinase dimerization Receptor Tyrosine Kinase Dimerization.jpg
Receptor tyrosine kinase dimerization

Receptor tyrosine kinase

Much like for G protein-coupled receptors, dimerization is essential for receptor tyrosine kinases (RTK) to perform their function in signal transduction, affecting many different cellular processes. [13] RTKs typically exist as monomers, but undergo a conformational change upon ligand binding, allowing them to dimerize with nearby RTKs. [14] [15] The dimerization activates the cytoplasmic kinase domains that are responsible for further signal transduction. [13]

See also

Related Research Articles

<span class="mw-page-title-main">G protein-coupled receptor</span> Class of cell surface receptors coupled to G-protein-associated intracellular signaling

G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily related proteins that are cell surface receptors that detect molecules outside the cell and activate cellular responses. They are coupled with G proteins. They pass through the cell membrane seven times in the form of six loops of amino acid residues, which is why they are sometimes referred to as seven-transmembrane receptors. Ligands can bind either to the extracellular N-terminus and loops or to the binding site within transmembrane helices. They are all activated by agonists, although a spontaneous auto-activation of an empty receptor has also been observed.

<span class="mw-page-title-main">Integrin</span> Instance of a defined set in Homo sapiens with Reactome ID (R-HSA-374573)

Integrins are transmembrane receptors that help cell–cell and cell–extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, organization of the intracellular cytoskeleton, and movement of new receptors to the cell membrane. The presence of integrins allows rapid and flexible responses to events at the cell surface.

<span class="mw-page-title-main">Protein kinase</span> Enzyme that adds phosphate groups to other proteins

A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them (phosphorylation) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a functional change of the target protein (substrate) by changing enzyme activity, cellular location, or association with other proteins. The human genome contains about 500 protein kinase genes and they constitute about 2% of all human genes. There are two main types of protein kinase. The great majority are serine/threonine kinases, which phosphorylate the hydroxyl groups of serines and threonines in their targets. Most of the others are tyrosine kinases, although additional types exist. Protein kinases are also found in bacteria and plants. Up to 30% of all human proteins may be modified by kinase activity, and kinases are known to regulate the majority of cellular pathways, especially those involved in signal transduction.

<span class="mw-page-title-main">Protein quaternary structure</span> Number and arrangement of multiple folded protein subunits in a multi-subunit complex

Protein quaternary structure is the fourth classification level of protein structure. Protein quaternary structure refers to the structure of proteins which are themselves composed of two or more smaller protein chains. Protein quaternary structure describes the number and arrangement of multiple folded protein subunits in a multi-subunit complex. It includes organizations from simple dimers to large homooligomers and complexes with defined or variable numbers of subunits. In contrast to the first three levels of protein structure, not all proteins will have a quaternary structure since some proteins function as single units. Protein quaternary structure can also refer to biomolecular complexes of proteins with nucleic acids and other cofactors.

<span class="mw-page-title-main">Signal transduction</span> Cascade of intracellular and molecular events for transmission/amplification of signals

Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events. Proteins responsible for detecting stimuli are generally termed receptors, although in some cases the term sensor is used. The changes elicited by ligand binding in a receptor give rise to a biochemical cascade, which is a chain of biochemical events known as a signaling pathway.

<span class="mw-page-title-main">Tyrosine kinase</span> Enzyme

A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions.

<span class="mw-page-title-main">Oligomer</span> Molecule composed of copies of a small unit

In chemistry and biochemistry, an oligomer is a molecule that consists of a few repeating units which could be derived, actually or conceptually, from smaller molecules, monomers. The name is composed of Greek elements oligo-, "a few" and -mer, "parts". An adjective form is oligomeric.

The JAK-STAT signaling pathway is a chain of interactions between proteins in a cell, and is involved in processes such as immunity, cell division, cell death, and tumor formation. The pathway communicates information from chemical signals outside of a cell to the cell nucleus, resulting in the activation of genes through the process of transcription. There are three key parts of JAK-STAT signalling: Janus kinases (JAKs), signal transducer and activator of transcription proteins (STATs), and receptors. Disrupted JAK-STAT signalling may lead to a variety of diseases, such as skin conditions, cancers, and disorders affecting the immune system.

<span class="mw-page-title-main">Major sperm protein</span>

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<span class="mw-page-title-main">Receptor tyrosine kinase</span> Class of enzymes

Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase proteins. Receptor tyrosine kinases have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Mutations in receptor tyrosine kinases lead to activation of a series of signalling cascades which have numerous effects on protein expression. The receptors are generally activated by dimerization and substrate presentation. Receptor tyrosine kinases are part of the larger family of protein tyrosine kinases, encompassing the receptor tyrosine kinase proteins which contain a transmembrane domain, as well as the non-receptor tyrosine kinases which do not possess transmembrane domains.

<span class="mw-page-title-main">Platelet-derived growth factor receptor</span> Cell surface receptors

Platelet-derived growth factor receptors (PDGF-R) are cell surface tyrosine kinase receptors for members of the platelet-derived growth factor (PDGF) family. PDGF subunits -A and -B are important factors regulating cell proliferation, cellular differentiation, cell growth, development and many diseases including cancer. There are two forms of the PDGF-R, alpha and beta each encoded by a different gene. Depending on which growth factor is bound, PDGF-R homo- or heterodimerizes.

<span class="mw-page-title-main">STAT5</span> Protein family

Signal transducer and activator of transcription 5 (STAT5) refers to two highly related proteins, STAT5A and STAT5B, which are part of the seven-membered STAT family of proteins. Though STAT5A and STAT5B are encoded by separate genes, the proteins are 90% identical at the amino acid level. STAT5 proteins are involved in cytosolic signalling and in mediating the expression of specific genes. Aberrant STAT5 activity has been shown to be closely connected to a wide range of human cancers, and silencing this aberrant activity is an area of active research in medicinal chemistry.

Pantothenate kinase (EC 2.7.1.33, PanK; CoaA) is the first enzyme in the Coenzyme A (CoA) biosynthetic pathway. It phosphorylates pantothenate (vitamin B5) to form 4'-phosphopantothenate at the expense of a molecule of adenosine triphosphate (ATP). It is the rate-limiting step in the biosynthesis of CoA.

The ErbB family of proteins contains four receptor tyrosine kinases, structurally related to the epidermal growth factor receptor (EGFR), its first discovered member. In humans, the family includes Her1, Her2 (ErbB2), Her3 (ErbB3), and Her4 (ErbB4). The gene symbol, ErbB, is derived from the name of a viral oncogene to which these receptors are homologous: erythroblastic leukemia viral oncogene. Insufficient ErbB signaling in humans is associated with the development of neurodegenerative diseases, such as multiple sclerosis and Alzheimer's disease, while excessive ErbB signaling is associated with the development of a wide variety of types of solid tumor.

<span class="mw-page-title-main">Histidine kinase</span> Family of enzymes important in cell signaling

Histidine kinases (HK) are multifunctional, and in non-animal kingdoms, typically transmembrane, proteins of the transferase class of enzymes that play a role in signal transduction across the cellular membrane. The vast majority of HKs are homodimers that exhibit autokinase, phosphotransfer, and phosphatase activity. HKs can act as cellular receptors for signaling molecules in a way analogous to tyrosine kinase receptors (RTK). Multifunctional receptor molecules such as HKs and RTKs typically have portions on the outside of the cell that bind to hormone- or growth factor-like molecules, portions that span the cell membrane, and portions within the cell that contain the enzymatic activity. In addition to kinase activity, the intracellular domains typically have regions that bind to a secondary effector molecule or complex of molecules that further propagate signal transduction within the cell. Distinct from other classes of protein kinases, HKs are usually parts of a two-component signal transduction mechanisms in which HK transfers a phosphate group from ATP to a histidine residue within the kinase, and then to an aspartate residue on the receiver domain of a response regulator protein. More recently, the widespread existence of protein histidine phosphorylation distinct from that of two-component histidine kinases has been recognised in human cells. In marked contrast to Ser, Thr and Tyr phosphorylation, the analysis of phosphorylated Histidine using standard biochemical and mass spectrometric approaches is much more challenging, and special procedures and separation techniques are required for their preservation alongside classical Ser, Thr and Tyr phosphorylation on proteins isolated from human cells.

<span class="mw-page-title-main">Cell surface receptor</span> Class of ligand activated receptors localized in surface of plama cell membrane

Cell surface receptors are receptors that are embedded in the plasma membrane of cells. They act in cell signaling by receiving extracellular molecules. They are specialized integral membrane proteins that allow communication between the cell and the extracellular space. The extracellular molecules may be hormones, neurotransmitters, cytokines, growth factors, cell adhesion molecules, or nutrients; they react with the receptor to induce changes in the metabolism and activity of a cell. In the process of signal transduction, ligand binding affects a cascading chemical change through the cell membrane.

<span class="mw-page-title-main">G beta-gamma complex</span>

The G beta-gamma complex (Gβγ) is a tightly bound dimeric protein complex, composed of one Gβ and one Gγ subunit, and is a component of heterotrimeric G proteins. Heterotrimeric G proteins, also called guanine nucleotide-binding proteins, consist of three subunits, called alpha, beta, and gamma subunits, or Gα, Gβ, and Gγ. When a G protein-coupled receptor (GPCR) is activated, Gα dissociates from Gβγ, allowing both subunits to perform their respective downstream signaling effects. One of the major functions of Gβγ is the inhibition of the Gα subunit.

<span class="mw-page-title-main">Protein dimer</span> Macromolecular complex formed by two, usually non-covalently bound, macromolecules

In biochemistry, a protein dimer is a macromolecular complex or multimer formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word dimer has roots meaning "two parts", di- + -mer. A protein dimer is a type of protein quaternary structure.

<span class="mw-page-title-main">Autophosphorylation</span>

Autophosphorylation is a type of post-translational modification of proteins. It is generally defined as the phosphorylation of the kinase by itself. In eukaryotes, this process occurs by the addition of a phosphate group to serine, threonine or tyrosine residues within protein kinases, normally to regulate the catalytic activity. Autophosphorylation may occur when a kinases' own active site catalyzes the phosphorylation reaction, or when another kinase of the same type provides the active site that carries out the chemistry. The latter often occurs when kinase molecules dimerize. In general, the phosphate groups introduced are gamma phosphates from nucleoside triphosphates, most commonly ATP.

<span class="mw-page-title-main">Tyrosine phosphorylation</span> Phosphorylation of peptidyl-tyrosine

Tyrosine phosphorylation is the addition of a phosphate (PO43−) group to the amino acid tyrosine on a protein. It is one of the main types of protein phosphorylation. This transfer is made possible through enzymes called tyrosine kinases. Tyrosine phosphorylation is a key step in signal transduction and the regulation of enzymatic activity.

References

  1. ↑ "Dimerization".
  2. ↑ Adar, Ram M.; Markovich, Tomer; Andelman, David (2017-05-17). "Bjerrum pairs in ionic solutions: A Poisson-Boltzmann approach". The Journal of Chemical Physics. 146 (19): 194904. arXiv: 1702.04853 . Bibcode:2017JChPh.146s4904A. doi:10.1063/1.4982885. ISSN   0021-9606. PMID   28527430. S2CID   12227786.
  3. ↑ Karle, J.; Brockway, L. O. (1944). "An Electron Diffraction Investigation of the Monomers and Dimers of Formic, Acetic and Trifluoroacetic Acids and the Dimer of Deuterium Acetate 1". Journal of the American Chemical Society. 66 (4): 574–584. doi:10.1021/ja01232a022. ISSN   0002-7863.
  4. ↑ Birks, J B (1975-08-01). "Excimers". Reports on Progress in Physics. 38 (8): 903–974. doi:10.1088/0034-4885/38/8/001. ISSN   0034-4885. S2CID   240065177.
  5. ↑ Shriver, Duward (2014). Inorganic Chemistry (6th ed.). W.H. Freeman and Company. pp. 306–307. ISBN   9781429299060.
  6. 1 2 3 4 Shriver, Duward (2014). Inorganic Chemistry (6th ed.). W.H. Freeman and Company. pp. 377–378. ISBN   9781429299060.
  7. ↑ Adams, Richard D.; Collins, Douglas E.; Cotton, F. Albert (1974). "Unusual structural and magnetic resonance properties of dicyclopentadienylhexacarbonyldichromium". Journal of the American Chemical Society. 96 (5): 749–754. doi:10.1021/ja00810a019.
  8. 1 2 Marianayagam, Neelan J.; Sunde, Margaret; Matthews, Jacqueline M. (2004). "The power of two: protein dimerization in biology". Trends in Biochemical Sciences. 29 (11): 618–625. doi:10.1016/j.tibs.2004.09.006. ISSN   0968-0004. PMID   15501681.
  9. ↑ Cooper, Geoffrey M. (2000). "Microtubules". The Cell: A Molecular Approach. 2nd Edition.
  10. ↑ Faron-Górecka, Agata; Szlachta, Marta; Kolasa, Magdalena; Solich, Joanna; Górecki, Andrzej; Kuśmider, Maciej; Żurawek, Dariusz; Dziedzicka-Wasylewska, Marta (2019-01-01), Shukla, Arun K. (ed.), "Chapter 10 - Understanding GPCR dimerization", Methods in Cell Biology, G Protein-Coupled Receptors, Part B, 149, Academic Press: 155–178, doi:10.1016/bs.mcb.2018.08.005, ISBN   9780128151075, PMID   30616817, S2CID   58577416 , retrieved 2022-10-27
  11. ↑ Rios, C. D.; Jordan, B. A.; Gomes, I.; Devi, L. A. (2001-11-01). "G-protein-coupled receptor dimerization: modulation of receptor function". Pharmacology & Therapeutics. 92 (2): 71–87. doi:10.1016/S0163-7258(01)00160-7. ISSN   0163-7258. PMID   11916530.
  12. ↑ Lohse, Martin J (2010-02-01). "Dimerization in GPCR mobility and signaling". Current Opinion in Pharmacology. GPCR. 10 (1): 53–58. doi:10.1016/j.coph.2009.10.007. ISSN   1471-4892. PMID   19910252.
  13. 1 2 Hubbard, Stevan R (1999-04-01). "Structural analysis of receptor tyrosine kinases". Progress in Biophysics and Molecular Biology. 71 (3): 343–358. doi: 10.1016/S0079-6107(98)00047-9 . ISSN   0079-6107. PMID   10354703.
  14. ↑ Lemmon, Mark A.; Schlessinger, Joseph (2010-06-25). "Cell Signaling by Receptor Tyrosine Kinases". Cell. 141 (7): 1117–1134. doi:10.1016/j.cell.2010.06.011. ISSN   0092-8674. PMC   2914105 . PMID   20602996.
  15. ↑ Lemmon, Mark A.; Schlessinger, Joseph; Ferguson, Kathryn M. (2014-04-01). "The EGFR Family: Not So Prototypical Receptor Tyrosine Kinases". Cold Spring Harbor Perspectives in Biology. 6 (4): a020768. doi: 10.1101/cshperspect.a020768 . ISSN   1943-0264. PMC   3970421 . PMID   24691965.
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