User:Ry19a/Leucine zipper

Leucine zipper

From Wikipedia, the free encyclopedia Jump to navigationJump to search"Overhead view", or helical wheel diagram, of a leucine zipper, where d represent amino acid leucine, arranged with other amino acids on two parallel alpha helices.

A leucine zipper (or leucine scissors) is a common three-dimensional structural motif in proteins. They were first described by Landschulz and collaborators in 1988 when they found that an enhancer binding protein had a very characteristic 30-amino acid segment and the display of these amino acid sequences on an idealized alpha helix revealed a periodic repetition of leucine residues at every seventh position over a distance covering eight helical turns. The polypeptide segments containing these periodic arrays of leucine residues were proposed to exist in an alpha-helical conformation and the leucine side chains from one alpha helix interdigitate with those from the alpha helix of a second polypeptide, facilitating dimerization.

Leucine zippers are a dimerization motif of the bZIP (Basic-region leucine zipper) class of eukaryotic transcription factors. The bZIP domain is 60 to 80 amino acids in length with a highly conserved DNA binding basic region and a more diversified leucine zipper dimerization region. The localization of the leucines are critical for the DNA binding to the proteins. Leucine zippers are present in both eukaryotic and prokaryotic regulatory proteins, but are mainly a feature of eukaryotes. They can also be annotated simply as ZIPs, and ZIP-like motifs have been found in proteins other than transcription factors and are thought to be one of the general protein modules for protein–protein interactions.

Contents

• 1Sequence and structure
• 2Specific binding between bZIP proteins and DNA
• 3Biology
• 4References
• 5External links

Sequence and structure[edit]

Another DNA binding domain, the Helix-loop-helix (HLH) dimer, is shown bound to a DNA fragment — each alpha helix represents a monomer.

(figure legend)(Note: This figure is wrong and should be delected)

Leucine zipper is created by the dimerization of two specific alpha helix monomers bound to DNA. The leucine zipper is formed by amphipathic interaction between two ZIP domains. The ZIP domain is found in the alpha-helix of each monomer, and contains leucines, or leucine-like amino acids. These amino acids are spaced out in each region's polypeptide sequence in such a way that when the sequence is coiled in a 3D alpha-helix, the leucine residues line up on the same side of the helix. This region of the alpha-helix- containing the leucines which line up- is called a ZIP domain, and leucines from each ZIP domain can weakly interact with leucines from other ZIP domains, reversibly holding their alpha-helices together (dimerization). When these alpha helices dimerize, the zipper is formed. The hydrophobic side of the helix forms a dimer with itself or another similar helix, burying the non-polar amino acids away from the solvent. The hydrophilic side of the helix interacts with the water in the solvent.

Leucine zipper motifs are considered a subtype of coiled coils, which are built by two or more alpha helices that are wound around each other to form a supercoil. Coiled coils contain 3- and 4-residue repeats whose hydrophobicity pattern and residue composition is compatible with the structure of amphipathic alpha-helices. The alternating three- and four-residue sequence elements constitute heptad repeats in which the amino acids are designated from a’ to g’. While residues in positions a and d are generally hydrophobic and form a zigzag pattern of knobs and holes that interlock with a similar pattern on another strand to form a tight-fitting hydrophobic core, residues in positions e and g are charged residues contributing to the electrostatic interaction.

In the case of leucine zippers, leucines are predominant at the d position of the heptad repeat. These residues pack against each other every second turn of the alpha-helices, and the hydrophobic region between two helices is completed by residues at the a positions, which are also frequently hydrophobic. They are referred to as coiled coils unless they are proven to be important for protein function. If that is the case, then they are annotated in the “domain” subsection, which would be the bZIP domain.

Two different types of such a-helices can pair up to form a heterodimeric leucine zipper. With apolar amino acid residues at either the e or g position, a heterotetramer consisting of 2 different leucine zippers can be generated in-vitro, which implies that the overall hydrophobicity of the interaction surface and van der vaals interaction may alter the organization of coiled coils and play a role in the formation of leucine zipper heterodimer.