GCM transcription factors
Encyclopedia
In molecular biology, the GCM transcription factors are a family of proteins
which contain a GCM motif
. The GCM motif is a domain
that has been identified in protein
s belonging to a family of transcriptional regulators involved in fundamental developmental processes which comprise Drosophila melanogaster
GCM and its mammalian homologues. In GCM transcription factors
the N-terminal moiety contains a DNA
-binding domain of 150 amino acid
s. Sequence conservation is highest in this GCM domain. In contrast, the C-terminal moiety contains one or two transactivating regions and is only poorly conserved
.
The GCM motif has been shown to be a DNA binding domain that recognises preferentially the nonpalindromic octamer 5'-ATGCGGGT-3'. The GCM motif contains many conserved
basic amino acid residues, seven cysteine
residues, and four histidine
residues. The conserved cysteines are involved in shaping the overall conformation of the domain, in the process of DNA binding and in the redox
regulation of DNA binding. The GCM domain as a new class of Zn
-containing DNA-binding domain with no similarity to any other DNA-binding domain. The GCM domain consists of a large and a small domain tethered together by one of the two Zn ion
s present in the structure
. The large and the small domains
comprise five- and three-stranded beta-sheets
, respectively, with three small helical segments packed against the same side of the two beta-sheets. The GCM domain exercises a novel mode of sequence-specific DNA recognition, where the five-stranded beta-pleated sheet inserts into the major groove of the DNA. Residues protruding from the edge strand of the beta-pleated sheet and the following loop
and strand contact the bases
and backbone of both DNA strands, providing specificity for its DNA target site.
Protein family
A protein family is a group of evolutionarily-related proteins, and is often nearly synonymous with gene family. The term protein family should not be confused with family as it is used in taxonomy....
which contain a GCM motif
Sequence motif
In genetics, a sequence motif is a nucleotide or amino-acid sequence pattern that is widespread and has, or is conjectured to have, a biological significance...
. The GCM motif is a domain
Protein domain
A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...
that has been identified in protein
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 belonging to a family of transcriptional regulators involved in fundamental developmental processes which comprise Drosophila melanogaster
Drosophila melanogaster
Drosophila melanogaster is a species of Diptera, or the order of flies, in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting from Charles W...
GCM and its mammalian homologues. In GCM transcription factors
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
the N-terminal moiety contains a 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...
-binding domain of 150 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. Sequence conservation is highest in this GCM domain. In contrast, the C-terminal moiety contains one or two transactivating regions and is only poorly conserved
Conserved sequence
In biology, conserved sequences are similar or identical sequences that occur within nucleic acid sequences , protein sequences, protein structures or polymeric carbohydrates across species or within different molecules produced by the same organism...
.
The GCM motif has been shown to be a DNA binding domain that recognises preferentially the nonpalindromic octamer 5'-ATGCGGGT-3'. The GCM motif contains many conserved
Conserved sequence
In biology, conserved sequences are similar or identical sequences that occur within nucleic acid sequences , protein sequences, protein structures or polymeric carbohydrates across species or within different molecules produced by the same organism...
basic amino acid residues, seven cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
residues, and four histidine
Histidine
Histidine Histidine, an essential amino acid, has a positively charged imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans...
residues. The conserved cysteines are involved in shaping the overall conformation of the domain, in the process of DNA binding and in the redox
Redox
Redox reactions describe all chemical reactions in which atoms have their oxidation state changed....
regulation of DNA binding. The GCM domain as a new class of Zn
Zinc
Zinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...
-containing DNA-binding domain with no similarity to any other DNA-binding domain. The GCM domain consists of a large and a small domain tethered together by one of the two Zn ion
Ion
An ion is an atom or molecule in which the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge. The name was given by physicist Michael Faraday for the substances that allow a current to pass between electrodes in a...
s present in the structure
Secondary structure
In biochemistry and structural biology, secondary structure is the general three-dimensional form of local segments of biopolymers such as proteins and nucleic acids...
. The large and the small domains
Protein domain
A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...
comprise five- and three-stranded beta-sheets
Beta sheet
The β sheet is the second form of regular secondary structure in proteins, only somewhat less common than the alpha helix. Beta sheets consist of beta strands connected laterally by at least two or three backbone hydrogen bonds, forming a generally twisted, pleated sheet...
, respectively, with three small helical segments packed against the same side of the two beta-sheets. The GCM domain exercises a novel mode of sequence-specific DNA recognition, where the five-stranded beta-pleated sheet inserts into the major groove of the DNA. Residues protruding from the edge strand of the beta-pleated sheet and the following loop
Turn (biochemistry)
A turn is an element of secondary structure in proteins where the polypeptide chain reverses its overall direction.- Definition :According to the most common definition, a turn is a structural motif where the Cα atoms of two residues separated by few peptide bonds are in close approach A turn is...
and strand contact the bases
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
and backbone of both DNA strands, providing specificity for its DNA target site.