Helix-turn-helix
Encyclopedia
In protein
s, the helix-turn-helix (HTH) is a major structural motif
capable of binding DNA
. It is composed of two α helices
joined by a short strand of amino acid
s and is found in many proteins that regulate gene expression
. It should not be confused with the helix-loop-helix domain.
Its discovery was based on similarities between the genes for Cro, CAP
, and λ repressor
, which share a common 20-25 amino acid
sequence that facilitates DNA recognition. In particular, recognition and binding to DNA is done by the two α helices, one occupying the N-terminal end of the motif, the other at the C-terminus. In most cases, such as in the Cro repressor, the second helix contributes most to DNA recognition, and hence it is often called the "recognition helix". It binds to the major groove of DNA through a series of hydrogen bond
s and various Van der Waals interactions with exposed bases
. The other α helix stabilizes the interaction between protein and DNA, but does not play a particularly strong role in its recognition.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s, the helix-turn-helix (HTH) is a major structural motif
Structural motif
In a chain-like biological molecule, such as a protein or nucleic acid, a structural motif is a supersecondary structure, which appears also in a variety of other molecules...
capable of binding DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
. It is composed of two α helices
Alpha helix
A common motif in the secondary structure of proteins, the alpha helix is a right-handed coiled or spiral conformation, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier...
joined by a short strand of amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s and is found in many proteins that regulate gene expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
. It should not be confused with the helix-loop-helix domain.
Its discovery was based on similarities between the genes for Cro, CAP
Catabolite Activator Protein
Catabolite Activator Protein or CAP is a transcriptional activator that exists as a homodimer in solution, with each subunit comprising a ligand-binding domain at the N-terminus , which is also responsible for the dimerization of the protein, and a DNA-binding domain at the C-terminus...
, and λ repressor
CI protein
cI protein , also known as the lambda repressor, is the sole protein expressed in the lysogenic state of Lambda phage. cI turns off transcription at the phage's L and R promoters as well as any other invading lambda phages into the host cell. It is a transcription factor and contains the common...
, which share a common 20-25 amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
sequence that facilitates DNA recognition. In particular, recognition and binding to DNA is done by the two α helices, one occupying the N-terminal end of the motif, the other at the C-terminus. In most cases, such as in the Cro repressor, the second helix contributes most to DNA recognition, and hence it is often called the "recognition helix". It binds to the major groove of DNA through a series of hydrogen bond
Hydrogen bond
A hydrogen bond is the attractive interaction of a hydrogen atom with an electronegative atom, such as nitrogen, oxygen or fluorine, that comes from another molecule or chemical group. The hydrogen must be covalently bonded to another electronegative atom to create the bond...
s and various Van der Waals interactions with exposed bases
Base pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...
. The other α helix stabilizes the interaction between protein and DNA, but does not play a particularly strong role in its recognition.
See also
- Winged helix turn helixWinged helix turn helixThe winged helix turn helix is a DNA-binding domain that binds to specific DNA sequences. It is formed by a 3-helical bundle and a 3- or 4-strand beta-sheet . Topology of helices and strands in the wHTH families may vary...
- DNA binding domain
- Secondary structureSecondary structureIn biochemistry and structural biology, secondary structure is the general three-dimensional form of local segments of biopolymers such as proteins and nucleic acids...
- Zinc fingerZinc fingerZinc fingers are small protein structural motifs that can coordinate one or more zinc ions to help stabilize their folds. They can be classified into several different structural families and typically function as interaction modules that bind DNA, RNA, proteins, or small molecules...
- DNA-binding proteinDNA-binding proteinDNA-binding proteins are proteins that are composed of DNA-binding domains and thus have a specific or general affinity for either single or double stranded DNA. Sequence-specific DNA-binding proteins generally interact with the major groove of B-DNA, because it exposes more functional groups that...
External links
- Helix-turn-helix motif, lambda-like repressor, from EMBL
- Full PDB entry for PDB ID 1LMB
- Cro/C1-type HTH domain, more HTHs in PROSITEPROSITEPROSITE is a protein database. It consists of entries describing the protein families, domains and functional sites as well as amino acid patterns, signatures, and profiles in them. These are manually curated by a team of the Swiss Institute of Bioinformatics and tightly integrated into Swiss-Prot...