The ATP-binding motif, also called the Walker motif, is a structural protein motif that is frequently found in proteins that bind ATP or GTP. It can usually be identified from just the primary structure of a protein using a fingerprint sequence that characterizes proteins as ATP or GTP-binding (see GTP-Binding Proteins). Walker et al. (1) identified two regions of sequence conservation: the A region has a stretch of small hydrophobic residues followed by [Gly/Ala]—X—X—Gly—X—Gly —Lys—Thr/Ser, where X is any residue. The second region of sequence conservation also has a stretch of small hydrophobic residues, this time ending in a conserved aspartate residue. In the three-dimensional structures of proteins having the ATP-binding motif, such as adenylate kinase, the hydrophobic residues of the A-region form a buried b-strand, and the glycine-rich region forms a loop, called the P-loop, that interacts with the phosphate of the bound nucleotide. The second conserved region codes for another hydrophobic b-strand, and the conserved aspartate is required for binding the magnesium ion that usually accompanies nucleotides bound to proteins.
The ATP-binding motif represents a common, but not the only, mode of interaction between proteins and ATP/GTP. For example, it is structurally distinct from the actin fold of proteins such as actin, hsp70, and hexokinase, which bind and hydrolyze ATP or GTP and where a conformational change is implicated in nucleotide binding (2).
