Walker motifs
Encyclopedia
The Walker A and Walker B motifs
are protein sequence motifs. These were first reported in ATP
-binding proteins by Walker
and co-workers in 1982.
-binding loop) is a motif in proteins. The motif has the pattern GXXXXGK(T/S), where G, K, T and S denote glycine
, lysine
, threonine
and serine
residues respectively, and X denotes any amino acid
. It is an ATP
or GTP
binding motif
found in many nucleotide
-binding protein
s. The lysine (K) residue in the Walker A motif is crucial for nucleotide-binding. It is a glycine
-rich loop preceded by a beta sheet
and followed by an alpha helix
. It interacts with the phosphate groups of the nucleotide
and with a magnesium
ion, which coordinates the β- and γ-phosphates.
Walker A motif is best known for its presence in nucleotide-binding proteins, but is also found in a variety of proteins with widely varying functions, including the alpha and beta subunits of ATP synthase
, myosin
, transducin
, helicase
s, kinases and RecA
.
Upon nucleotide hydrolysis the loop does not significantly change conformation
, but stays bound to the remaining phosphate groups. Walker motif A-binding has been shown to cause structural changes in the bound nucleotide, along the line of the induced fit model of enzyme
binding.
PTPs (protein tyrosine phosphatases) that catalyse the hydrolysis of an inorganic phosphate from a phosphotyrosine residue (the reverse of a tyrosine kinase
reaction) also contain a motif which folds into a P-loop-like structure. The conserved sequence of this motif is CXXXXXR(S/T), where C and R denote cysteine
and arginine
residues respectively.
ring of ATP) is a conserved subdomain of aromatic amino acids, found approximately 25 amino acids upstream of the Walker A motif. This subdomain is essential for ATP-binding.
in proteins. Walker et al reported the consensus sequence of this motif to be (R/K)XXXXGXXXXLhhhhD, where R, K, G, L and D denote arginine
, lysine, glycine, L leucine
, and aspartic acid
residues respectively, X represents any of the 20 standard amino acids and h denotes a hydrophobic amino acid. The consensus sequence of this motif was more recently reported by Hanson et al. to be hhhhDE, where E denotes a glutamate residue. The aspartate and glutamate also form a part of the DEAD/DEAH
motifs found in helicases. The aspartate residue co-ordinates magnesium ions, and the glutamate is essential for ATP hydrolysis.
There is considerable variability in the sequence of this motif, with the only invariant features being a negatively charged residue following a stretch of bulky, hydrophobic amino acids.
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...
are protein sequence motifs. These were first reported in ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
-binding proteins by Walker
John E. Walker
Professor Sir John Ernest Walker is an English chemist who won the Nobel Prize in Chemistry in 1997. He is currently the director of the MRC Mitochondrial Biology Unit in Cambridge, and a Fellow of Sidney Sussex College.He was born in Halifax, Yorkshire, the son of Thomas Ernest Walker, a...
and co-workers in 1982.
Walker A motif
Walker A motif, also known as the Walker loop or P-loop (phosphatePhosphate
A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...
-binding loop) is a motif in proteins. The motif has the pattern GXXXXGK(T/S), where G, K, T and S denote glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
, lysine
Lysine
Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
, threonine
Threonine
Threonine is an α-amino acid with the chemical formula HO2CCHCHCH3. Its codons are ACU, ACA, ACC, and ACG. This essential amino acid is classified as polar...
and serine
Serine
Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...
residues respectively, and X denotes any 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...
. It is an ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
or GTP
Guanosine triphosphate
Guanosine-5'-triphosphate is a purine nucleoside triphosphate. It can act as a substrate for the synthesis of RNA during the transcription process...
binding 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...
found in many nucleotide
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...
-binding 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. The lysine (K) residue in the Walker A motif is crucial for nucleotide-binding. It is a glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
-rich loop preceded by a beta sheet
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...
and followed by an alpha helix
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...
. It interacts with the phosphate groups of the nucleotide
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 with a magnesium
Magnesium
Magnesium is a chemical element with the symbol Mg, atomic number 12, and common oxidation number +2. It is an alkaline earth metal and the eighth most abundant element in the Earth's crust and ninth in the known universe as a whole...
ion, which coordinates the β- and γ-phosphates.
Walker A motif is best known for its presence in nucleotide-binding proteins, but is also found in a variety of proteins with widely varying functions, including the alpha and beta subunits of ATP synthase
ATP synthase
right|thumb|300px|Molecular model of ATP synthase by X-ray diffraction methodATP synthase is an important enzyme that provides energy for the cell to use through the synthesis of adenosine triphosphate . ATP is the most commonly used "energy currency" of cells from most organisms...
, myosin
Myosin
Myosins comprise a family of ATP-dependent motor proteins and are best known for their role in muscle contraction and their involvement in a wide range of other eukaryotic motility processes. They are responsible for actin-based motility. The term was originally used to describe a group of similar...
, transducin
Transducin
Transducin is a heterotrimeric G protein that is naturally expressed in vertebrate retina rods and cones .- Mechanism of action :...
, helicase
Helicase
Helicases are a class of enzymes vital to all living organisms. They are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separating two annealed nucleic acid strands using energy derived from ATP hydrolysis.-Function:Many cellular processes Helicases are a...
s, kinases and RecA
RecA
RecA is a 38 kilodalton Escherichia coli protein essential for the repair and maintenance of DNA. RecA has a structural and functional homolog in every species in which it has been seriously sought and serves as an archetype for this class of homologous DNA repair proteins...
.
Upon nucleotide hydrolysis the loop does not significantly change conformation
Conformational change
A macromolecule is usually flexible and dynamic. It can change its shape in response to changes in its environment or other factors; each possible shape is called a conformation, and a transition between them is called a conformational change...
, but stays bound to the remaining phosphate groups. Walker motif A-binding has been shown to cause structural changes in the bound nucleotide, along the line of the induced fit model of enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
binding.
PTPs (protein tyrosine phosphatases) that catalyse the hydrolysis of an inorganic phosphate from a phosphotyrosine residue (the reverse of a tyrosine kinase
Tyrosine kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a protein in a cell. It functions as an "on" or "off" switch in many cellular functions....
reaction) also contain a motif which folds into a P-loop-like structure. The conserved sequence of this motif is CXXXXXR(S/T), where C and R denote 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...
and arginine
Arginine
Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...
residues respectively.
A-loop
The A-loop (Aromatic residue interacting with the AdenineAdenine
Adenine is a nucleobase with a variety of roles in biochemistry including cellular respiration, in the form of both the energy-rich adenosine triphosphate and the cofactors nicotinamide adenine dinucleotide and flavin adenine dinucleotide , and protein synthesis, as a chemical component of DNA...
ring of ATP) is a conserved subdomain of aromatic amino acids, found approximately 25 amino acids upstream of the Walker A motif. This subdomain is essential for ATP-binding.
Walker B motif
Walker B motif is a motifStructural 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...
in proteins. Walker et al reported the consensus sequence of this motif to be (R/K)XXXXGXXXXLhhhhD, where R, K, G, L and D denote arginine
Arginine
Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...
, lysine, glycine, L leucine
Leucine
Leucine is a branched-chain α-amino acid with the chemical formula HO2CCHCH2CH2. Leucine is classified as a hydrophobic amino acid due to its aliphatic isobutyl side chain. It is encoded by six codons and is a major component of the subunits in ferritin, astacin and other 'buffer' proteins...
, and aspartic acid
Aspartic acid
Aspartic acid is an α-amino acid with the chemical formula HOOCCHCH2COOH. The carboxylate anion, salt, or ester of aspartic acid is known as aspartate. The L-isomer of aspartate is one of the 20 proteinogenic amino acids, i.e., the building blocks of proteins...
residues respectively, X represents any of the 20 standard amino acids and h denotes a hydrophobic amino acid. The consensus sequence of this motif was more recently reported by Hanson et al. to be hhhhDE, where E denotes a glutamate residue. The aspartate and glutamate also form a part of the DEAD/DEAH
DEAD box
DEAD box proteins are involved in an assortment of metabolic processes that involve RNA. They are highly conserved in nine domains and can be found in both prokaryotes and eukaryotes, but not all...
motifs found in helicases. The aspartate residue co-ordinates magnesium ions, and the glutamate is essential for ATP hydrolysis.
There is considerable variability in the sequence of this motif, with the only invariant features being a negatively charged residue following a stretch of bulky, hydrophobic amino acids.