Coiled coil

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Figure 1: The classic example of a coiled coil is the GCN4 leucine zipper (PDB accession code 1zik), which is a parallel, left-handed homodimer. However, many other types of coiled coil exist.

A coiled coil is a structural motif in which 2-6 alpha-helices are coiled together like the strands of a rope. (Dimers and trimers are the most common types.) The α-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.^[1]

[edit] Tertiary and quaternary structure of coiled coils

Coiled coils usually contain a repeated seven residue pattern called heptad repeats.

[edit] Molecular interactions stabilizing coiled coils

Coiled coils are held together by hydrophobic forces. When two or more alpha-helices have repeating patterns of hydrophobic amino acid side chains, the most favorable way for them to conform in the water-filled environment of the cytoplasm is to wrap the hydrophobic strands against each other sandwiched between the hydrophilic amino acids.

[edit] Biological roles of coiled coils

Coiled coils often function as dimerization "tags".

The protein tropomyosin is also a parallel coiled coil.

[edit] Role of coiled coils in HIV infection

Side view of the gp41 hexamer that initiates the entry of HIV into its target cell.

A key step in the entry of HIV into human cells is the exposure of a trimeric, parallel coiled coil known as gp41. The gp41 trimer is normally covered by another surface glycoprotein known as gp120, 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.

[edit] History of coiled coils

The possibility of coiled coils was proposed (1952) soon after the structure of the alpha helix (1951), as well as mathematical methods for determining their structure.

[edit] References

[edit] Additional references

• Crick FHC. (1952) Nature, 170. 882.

• Pauling L and Corey RB. (1953) "Compound Helical Configurations of Polypeptide Chains: Structure of Proteins of the α-Keratin Type", Nature, 171, 59-61.

• Crick FHC. (1953) "The Packing of α-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.

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