An ATP-binding motif is a 250-residue sequence within an ATP-binding protein’s primary structure. The binding motif is associated with a protein’s structure and/or function. ATP is a molecule of energy, and can be a coenzyme, involved in a number of biological reactions. ATP is proficient at interacting with other molecules through a binding site. The ATP binding site is the environment in which ATP catalytically actives the

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

and, as a result, is hydrolyzed to ADP. The binding of ATP causes a conformational change to the enzyme it is interacting with. The genetic and functional similarity of such a motif demonstrates micro-evolution: proteins have co-opted the same binding sequence from other enzymes rather than developing them independently. ATP binding sites, which may be representative of an ATP binding motif, are present in many proteins which require an input of energy (from ATP), such sites as active membrane transporters,

microtubule Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 an ...

subunits,

flagellum A flagellum (; ) is a hairlike appendage that protrudes from certain plant and animal sperm cells, and from a wide range of microorganisms to provide motility. Many protists with flagella are termed as flagellates. A microorganism may have f ...

proteins, and various hydrolytic and

proteolytic Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called proteases, ...

enzymes.

Primary sequence

The short motifs involving ATP-binding are the

Walker motifs The Walker A and Walker B motifs are protein sequence motifs, known to have highly conserved three-dimensional structures. These were first reported in ATP-binding proteins by Walker and co-workers in 1982. Of the two motifs, the A motif is ...

, Walker A, also known as the P-loop, and Walker B, as well as the C motif and switch motif.

Walker A motif

The Walker site A has a primary amino acid sequence of or . The letter can represent any amino acid.

Walker B motif

The primary amino acid sequence of the Walker B site is , in which represents any

hydrophobic In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, th ...

amino acid.

C motif

The C motif, also known as the signature motif, LSGGQ motif, or the linker peptide, has a primary amino acid sequence of . Due to the variety of different amino acids that can be used in the

primary sequence Biomolecular structure is the intricate folded, three-dimensional shape that is formed by a molecule of protein, DNA, or RNA, and that is important to its function. The structure of these molecules may be considered at any of several length sc ...

, of both the Walker site A and B, the non-variant amino acids within the sequence are highly conserved. A mutation of any of these amino acids will affect the binding ATP or interfere with the catalytic activity of the enzyme. The primary amino acid sequence determines the three dimensional structure of each motif.

Structure

All of the ATP binding domains are made up of an estimated 250 residues and two subunits, creating a

dimer Dimer may refer to: * Dimer (chemistry), a chemical structure formed from two similar sub-units ** Protein dimer, a protein quaternary structure ** d-dimer * Dimer model, an item in statistical mechanics, based on ''domino tiling'' * Julius Dimer ...

. These residues are folded into six α-helices and five β-strands. Abc domain

Walker A motif

Structurally, the Walker A motif consists of an

α-helix The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues e ...

and is always followed by a glycine-rich loop.

Walker B motif

The Walker B motif is a

β-strand 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 g ...

. The Walker motifs are connected to each other by a peptide sequence of about 100 residues. Structurally, these connecting residues fold into an α-helical domain.

C motif

Directly following the Walker B motif, is the signature motif.

Switch motif

The switch motif has been found to be located at the end of the β4-strand in ATP-binding proteins.

Function

Each ATP binding motif has a different role to play whether it is directly involved with the binding of ATP or helping with the construction of the ATP-binding cassette (ABC) transporter. The ATP molecule binds to the connecting point of each subunit of the dimer, indicating that ATP is in close proximity to both subunits during catalysis. The two binding motifs that ATP directly interacts with is the residues from the Walker A motif, located on one of the subunits, and the residues from the C binding motif, located on the other subunit. The Walker A binding motif has a

lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −C ...

side chain, which is essential for the binding of ATP. The lysine residue forms hydrogen bonds with the oxygen atoms of two phosphate groups within ATP, therefore creating proximity and orientation of ATP in the binding site. In order for the Walker A motif to bind to ATP, the ATP molecule must be in the binding site. The signature motif acts as a signal to the Walker A motif, letting the Walker A know when the ATP molecule has bound to the binding site. The signature motif does this by allowing its residues to extend from the subunit they are located into the other subunit where the Walker A motif is. It is necessary that ATP binds to both nucleotide binding domains in order to complete the catalytically active structure. The Walker B motif contains the amino acid

glutamate Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...

within the short sequence. Glutamate can be used to perform a

nucleophilic attack In chemistry, a nucleophile is a chemical species that forms bonds by donating an electron pair. All molecules and ions with a free pair of electrons or at least one pi bond can act as nucleophiles. Because nucleophiles donate electrons, they are ...

on the ATP molecule. Found in the switch binding motif is a

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 de ...

residue. The function of the histidine is to influence the reaction catalytically by contacting the residues across the dimer interface, including the Walker A motif and the Walker B motif. It is the histidine residue that forms the tight coupling between the binding of the ATP molecule and the dimer. Following the hydrolysis of ADP, a

conformational change In biochemistry, a conformational change is a change in the shape of a macromolecule, often induced by environmental factors. A macromolecule is usually flexible and dynamic. Its shape can change in response to changes in its environment or oth ...

must occur to separate the ATP-binding cassette. This separation is driven by an

electrostatic repulsion Electrostatics is a branch of physics that studies electric charges at rest ( static electricity). Since classical times, it has been known that some materials, such as amber, attract lightweight particles after rubbing. The Greek word for a ...

by the ADP product that is bound the Walker A motif and the inorganic phosphate product is bound to the C motif.

References

{{Reflist Protein domains