Coiled coil

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Coiled coil

For the coiled coil shape in general, see coil
Coil

A coil is a series of wiktionary:loops. A coiled coil is a structure where the coil itself is in turn also looping....
.

A coiled coil is a structural motif

Structural motif

In an unbranched, polymer biological molecule, such as a protein or a strand of RNA, a structural motif is a three-dimensional structural element or protein folding within the chain, which appears also in a variety of other molecules....
in protein

Protein

Proteins are organic compounds made of amino acids arranged in a linear chain and joined together by peptide bonds between the carboxyl and amino groups of adjacent amino acid Residue ....
s, in which 2-7 alpha-helices

Alpha helix

A common motif in the secondary structure of proteins, the alpha helix is a right- or left-handed coiled conformation, resembling a spring , in which every backbone amino group donates a hydrogen bond to the backbone carbonyl group of the amino acid four residues earlier ....
are coiled together like the strands of a rope (Dimers

Dimer

File:Carboxylic acid dimers.pngA dimer is a chemical or biological entity consisting of two identical subunits called monomers, which are held together by either intramolecular forces or weaker intermolecular forces....
and trimer

Trimer

Trimer might refer to:* trimer , a reaction product composed of three identical molecules* trimer , a compound of three macromolecules non-covalently bound...
s are the most common types).

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Encyclopedia

For the coiled coil shape in general, see coil
Coil

A coil is a series of wiktionary:loops. A coiled coil is a structure where the coil itself is in turn also looping....
.

A coiled coil is a structural motif

Structural motif

Protein

Alpha helix

Dimer

Trimer

Trimer might refer to:* trimer , a reaction product composed of three identical molecules* trimer , a compound of three macromolecules non-covalently bound...
s are the most common types). Many coiled coil type proteins are involved in important biological functions such as the regulation of gene expression

Gene expression

Gene expression is the process by which inheritable information from a gene, such as the DNA sequence, is made into a functional gene product, such as protein or RNA....
e.g. transcription factor

Transcription factor

In the field of molecular biology, a transcription factor is a protein that binds to specific DNA sequence and thereby controls the transfer of genetic information from DNA to RNA....
s. Notable examples are the proteins the oncoproteins c-fos and jun, and the muscle protein tropomyosin

Tropomyosin

Tropomyosin is an actin-binding protein that regulates actin mechanics. It is important, among other things, for muscle contraction. Tropomyosin, along with the troponin complex, associate with actin in muscle fibers and regulate muscle contraction by regulating the binding of myosin....
.

Molecular structure of coiled coils

Coiled coils usually contain a repeated seven amino acid

Amino acid

In chemistry, an amino acid is a molecule containing both amine and carboxyl functional groups. These molecules are particularly important in biochemistry, where this term refers to alpha-amino acids with the general formula H2NCHRCOOH, where R is an organic substituent....
residue pattern called heptad repeat

Heptad repeat

The heptad repeat is an example of a structural motif which consists of a repeating pattern of amino acids: a b c d e f g H P P H P P P...
s. The interacting surface between the helices often contain hydrophobic residues, such as leucine

Leucine

Leucine is an a-amino acid with the chemical formula HO2CCHCH2CH2. It is an essential amino acid, which means that humans cannot synthesise it....
arranged in a so called leucine zipper

Leucine zipper

A leucine zipper, aka leucine scissors, is a super secondary structural motif found in proteins that creates adhesion forces in parallel alpha helices....
. The most favorable way for two such helices to arrange themselves in the water-filled environment of the cytoplasm

Cytoplasm

The cytoplasm is the part of a Cell that is enclosed within the plasma membrane. In eukaryote cells the cytoplasm contains organelles, such as mitochondrion, that are filled with liquid kept separate from the rest of the cytoplasm by biological membranes....
is to wrap the hydrophobic strands against each other sandwiched between the hydrophilic amino acids. It is thus the burial of hydrophobic surfaces, that provides the thermodynamic driving force for the oligomerization.

The a-helices may be parallel or antiparallel, and usually adopt a left-handed super-coil (Figure 1). Although disfavored, a few right-handed coiled coils have also been observed in nature and in designed proteins.

Biological roles of coiled coils

Role of coiled coils in HIV infection

A key step in the entry

Viral entry

Viral entry is the earliest stage of infection in the viral life cycle, as the virus comes into contact with the host cell and introduces viral material into the cell....
of HIV

HIV

Human immunodeficiency virus is a lentivirus that can lead to AIDS , a condition in humans in which the immune system begins to fail, leading to life-threatening opportunistic infections....
into human cells is the exposure of a trimeric, parallel coiled coil known as gp41

Gp41

gp41 is a glycoprotein non-covalent bond-bound to gp120, and provides the second step by which viral entry the cell. It is originally buried within the virus envelope, but, when gp120 binds to a CD4 receptor, gp120 changes its Conformational isomerism, causing gp41 to become exposed, where it can assist in fusion with the host cell....
. The gp41 trimer is normally covered by another surface glycoprotein known as gp120

Gp120

gp120 is a glycoprotein exposed on the surface of the HIV structure and genome. The 120 in its name comes from its molecular weight of 120 Dalton ....
, which protects it from antibodies. Upon binding to the target cell, gp120 undergoes a conformational change that exposes the gp41 trimer, whose hydrophobic N-terminal tails enter the target cell membrane. Three other helices of gp41 fold down into the grooves of the gp41 coiled coil trimer, forming a hexamer, and drawing the viral membrane and target-cell membrane close enough to fuse. The virus then enters the cell and begins its replication. Recently, inhibitors that bind in the gp41 grooves have been developed, such as Fuzeon

Enfuvirtide

Enfuvirtide is an HIV fusion inhibitor, the first of a novel class of antiretroviral drugs used in combination therapy for the treatment of HIV-1 infection....
.

Coiled coils as dimerization tags

Because of their specific interaction coiled coils can be used as a dimerization "tag".

History of coiled coils

The possibility of coiled coils for a-keratin

Keratin

Keratins are a family of fibrous protein; tough and insoluble, they form the hard but mineral structures found in reptiles, birds, amphibians and mammals....
was proposed by Francis Crick

Francis Crick

Francis Harry Compton Crick Order of Merit Royal Society , Ph.D., was a British molecular biology, physics, and neuroscience, and most noted for being one of the co-discoverers of the structure of the DNA molecule in 1953....
in 1952 as well as mathematical methods for determining their structure. Remarkably, this was soon after the structure of the alpha helix

Alpha helix

Linus Pauling

Linus Carl Pauling was an United States scientist, peace activist, author and list of educators. He was one of the most influential chemists in history and ranks among the most important scientists in any field of the 20th century....
and coworkers.

Software to predict coiled-coils

contains an algorithm to predict coiled-coils from AA-sequences
/

Additional references

Crick FHC. (1953) "The Packing of a-Helices: Simple Coiled-Coils", Acta Cryst., 6, 689-697.
Nishikawa K. and Scheraga HA. (1976) "Geometrical Criteria for Formation of Coiled-Coil Structures of Polypeptide Chains", Macromolecules, 9, 395-407.
Harbury PB, Zhang T, Kim PS and Alber T. (1993) "A Switch Between Two-, Three-, and Four-Stranded Coiled Coils in GCN4 Leucine Zipper Mutants", Science, 262, 1401-1407.
Gonzalez L, Plecs JJ and Alber T. (1996) "An engineered allosteric switch in leucine-zipper oligomerization", Nature Structural Biology, 3, 510-515.
Harbury PB, Plecs JJ, Tidor B, Alber T and Kim PS. (1998) "High-Resolution Protein Design with Backbone Freedom", Science, 282, 1462-1467.
Yu YB. (2002) "Coiled-coils: stability, specificity, and drug delivery potential", Adv. Drug Deliv. Rev., 54, 1113-1129.
Burkhard P, Ivaninskii S and Lustig A. (2002) "Improving Coiled-coil Stability by Optimizing Ionic Interactions", Journal of Molecular Biology, 318, 901-910.
Gillingham AK and Munro S. (2003) "Long coiled-coil proteins and membrane traffic.", Biochim. Biophys. Acta, 1641, 71-85.
Mason JM and Arndt KM, (2004) "Coiled coil domains: stability, specificity, and biological implications", Chembiochem, 5, 170-6.