Question

Define leucine zipper, helix-turn-helix, helix-loop-helix, and zinc finger, and explain why each is stable.

Define the following domains: SH2, SH3, Bromo, Chromo, PTB, SNARE, EF-Hand?

Answer 1

DNA binding domains that bind to DNA can regulate the process of transcription

1.  leucine zipper

motif present in the DNA-binding domains of a large class of transcription factors contains the hydrophobic amino acid leucine at every seventh position in the sequence. These proteins bind to DNA as dimers, and mutagenesis of the leucines showed that they were required for dimerization. Consequently, the name leucine zipper was coined to denote this structural motif of a coiled coil of two α helixes.
2. helix-turn-helix

The helix turn helix motif consists of 20 residues characterized by two alpha helices, which makes it contact with DNA. The second helix contacts the DNA through hydrogen bonding and hydrophobic interactions which occur between specific side chains and the exposed bases and thymine methyl groups within the major groove of the DNA.
3. helix-loop-helix

The DNA-binding domain of another class of dimeric transcription factors contains a structural motif that is very similar to the basic zipper motif except that a nonhelical loop of the polypeptide chain separates two α-helical regions in each monomer. Termed a basic helix-loop-helix (bHLH), this motif was predicted from the amino acid sequences of these proteins, which contain an N-terminal α helix with basic residues that interact with DNA, a middle loop region, and a C-terminal region, with hydrophobic amino acids spaced at intervals characteristic of an amphipathic α helix, that dimerizes into a coiled coil.

4.  zinc finger

Eukaryotic proteins have regions that fold around a central Zn2+ ion, producing a compact domain from a relatively short length of polypeptide compact domain from a relatively short length of the polypeptide chain. The C2H2 zinc finger is the most common DNA-binding motif encoded in the human genome and the genomes of other mammals. This motif has a 23–26-residue consensus sequence containing two conserved cysteines (C) and two conserved histidines (H) residues, whose side chains bind one Zn2+ ion.

src homology domain (SH2) is a sequence-specific phosphotyrosine-binding module present in signaling molecule.  In cytoplasmic tyrosine kinases, the SH2 domain is located N-terminally to the catalytic kinase domain where it mediates cellular localization, substrate recruitment, and regulation of kinase activity. The SH3 domain is a distinct motif that binds target proteins, including proteins associated with the actin cytoskeleton, through sequences containing proline and hydrophobic amino acids. Proteins encoding phosphotyrosine binding (PTB) domains function as adaptors or scaffolds to organize the signaling complexes involved in wide-ranging physiological processes including neural development, immunity, tissue homeostasis and cell growth. SNAREs are key proteins involved in vesicle fusion the membranes of the vesicle
and target compartment come into close contact with one another as the result of an interaction between the cytosolic regions of integral proteins of the two membranes. SNAREs can be divided functionally into two categories, v‐SNAREs, which become incorporated into the membranes of transport vesicles during budding, and t‐SNAREs, which are located in the membranes of target compartments. EF-Hand domains The EF-hand motif contains approximately 40 residues and is involved in binding intracellular calcium.  The binding of calcium to regulatory EF-hand domain—containing proteins induces a conformational change that is transmitted to their target proteins