In molecular biology, the GCM transcription factors are a family of proteins which contain a GCM

motif Motif may refer to: General concepts * Motif (chess composition), an element of a move in the consideration of its purpose * Motif (folkloristics), a recurring element that creates recognizable patterns in folklore and folk-art traditions * Moti ...

. The GCM motif is a

domain Domain may refer to: Mathematics *Domain of a function, the set of input values for which the (total) function is defined ** Domain of definition of a partial function **Natural domain of a partial function **Domain of holomorphy of a function *Do ...

that has been identified in

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...

s belonging to a family of

transcriptional regulators Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products (protein or RNA). Sophisticated programs of gene expression are wide ...

involved in fundamental developmental processes which comprise ''

Drosophila melanogaster ''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the " vinegar fly" or " pomace fly". Starting with ...

'' GCM and its

mammalian Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...

homologues (human

GCM1 Chorion-specific transcription factor GCMa is a protein that, in humans, is encoded by the ''GCM1'' gene. This gene encodes a DNA-binding protein with a gcm-motif ( glial cell missing motif). The encoded protein is a homolog of the '' Drosoph ...

and GCM2). In GCM

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...

s the

N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

moiety contains a DNA-binding domain of 150

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...

Sequence conservation In evolutionary biology, conserved sequences are identical or similar Sequence (biology), sequences in nucleic acids (DNA sequence, DNA and RNA) or peptide sequence, proteins across species (homology (biology)#Orthology, orthologous sequences), ...

is highest in this GCM domain. In contrast, the

C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...

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 Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, s ...

residues, and four

histidine Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the ...

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 (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate (chemistry), substrate change. Oxidation is the loss of Electron, electrons or an increase in the oxidation state, while reduction ...

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 An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conven ...

s present in the structure. The large and the small domains comprise five- and three-stranded beta-sheets, respectively, with three small

helical Helical may refer to: * Helix A helix () is a shape like a corkscrew or spiral staircase. It is a type of smooth space curve with tangent lines at a constant angle to a fixed axis. Helices are important in biology, as the DNA molecule is ...

segments packed against the same side of the two

beta-sheet The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a gen ...

s. The GCM domain exercises a novel mode of sequence-specific DNA recognition, where the five-stranded beta-pleated sheet inserts into the

major groove Major (commandant in certain jurisdictions) is a military rank of commissioned officer status, with corresponding ranks existing in many military forces throughout the world. When used unhyphenated and in conjunction with no other indicators ...

of the DNA. Residues protruding from the edge strand of the beta-pleated sheet and the following

loop Loop or LOOP may refer to: Brands and enterprises * Loop (mobile), a Bulgarian virtual network operator and co-founder of Loop Live * Loop, clothing, a company founded by Carlos Vasquez in the 1990s and worn by Digable Planets * Loop Mobile, ...

and strand contact the bases and backbone of both DNA strands, providing specificity for its DNA target site.

References

{{InterPro content, IPR003902 Protein families