Ankyrin Repeat:  A Unique Motif Mediating Protein−Protein Interactions

Abstract

Ankyrin repeat, one of the most widely existing protein motifs in nature, consists of 30−34 amino acid residues and exclusively functions to mediate protein−protein interactions, some of which are directly involved in the development of human cancer and other diseases. Each ankyrin repeat exhibits a helix−turn−helix conformation, and strings of such tandem repeats are packed in a nearly linear array to form helix−turn−helix bundles with relatively flexible loops. The global structure of an ankyrin repeat protein is mainly stabilized by intra- and inter-repeat hydrophobic and hydrogen bonding interactions. The repetitive and elongated nature of ankyrin repeat proteins provides the molecular bases of the unique characteristics of ankyrin repeat proteins in protein stability, folding and unfolding, and binding specificity. Recent studies have demonstrated that ankyrin repeat proteins do not recognize specific sequences, and interacting residues are discontinuously dispersed into the whole molecules of both the ankyrin repeat protein and its partner. In addition, the availability of thousands of ankyrin repeat sequences has made it feasible to use rational design to modify the specificity and stability of physiologically important ankyrin repeat proteins and even to generate ankyrin repeat proteins with novel functions through combinatorial chemistry approaches.

Mitochondrial localization and structure-based phosphate activation mechanism of Glutaminase C with implications for cancer metabolism

“…A possible explanation however, might come from the C-terminal portions, which share only 12% sequence identity. KGA is predicted to contain three ankyrin repeats which exclusively function to mediate protein-protein interactions and have been found in proteins of diverse function such as cell-cycle regulators, transcriptional initiators, cytoskeletal proteins, ion transporters, and signal transducers (32). Furthermore, aside from the N-terminal NR box motif in all three glutaminase isozymes, as the structure of GAC presented here confirms, the last five amino acids in the KGA sequence (LDGLL) may also serve as a second NR box.…”

Regulation of Nuclear Translocation of the Myb1 Transcription Factor by TvCyclophilin 1 in the Protozoan Parasite Trichomonas vaginalis

“…Such an enzyme-independent binding activity is not unusual as it is also seen in hCyPA in which the conserved Arg 55 that is essential for enzyme activity is not involved in binding to CD147 (29). Hsp70 in human cells can bind to the tetratricopeptide repeats in the C terminus of hCyP40 to assist in the formation of an inactivated multicomponent steroid receptor (51), whereas the enzyme activity of hCyPA catalyzes the proper folding of ankyrin repeats in a protein for the assembly of protein complexes (52,53). Although TvCyP1 has no functional domain other than the CLD, it may exploit TvAnk-1 as a scaffold for the assembly of the TvCyP1-Myb1 protein complex on vesicle surfaces, and TvHsp70-1 likely serves as a co-chaperone for TvCyP1 for conformational changes in unknown targets.…”

ANK6, a mitochondrial ankyrin repeat protein, is required for male-female gamete recognition in Arabidopsis thaliana

“…Ankyrins are characterized by a widely occurring repeat motif of 33 amino acid residues (22) and are believed to act in proteinprotein interactions (23)(24)(25). We show that the mutant in an ankyrin repeat gene, ANK6, has a phenotype in that it impairs male-female gamete recognition.…”