| 摘要 |
<p>The association between ankyrin and α-Na,K-ATPase, a ubiquitous membrane protein critical to vectorial transport of ions and nutrients, is required to assemble and stabilize Na,K-ATPase at the membrane. The present invention is drawn to the disclosure that α-Na,K-ATPase binds both red cell (ANK1) and Madin Darby Canine Kidney (MDCK) cell ankyrin (ANK3) predominantly by residues 142-166 (the minimal ankyrin binding domain), located within its second putative cytoplasmic domain. Fusion peptides of glutathione-S-transferase incorporating these residues bind specifically to ankyrin. For the first time, the three-dimensional structure (2.6 Å) of the minimal binding domain of the fusion peptide reveals a 7 residue loop with one charged hydrophilic face capping a double β-strand. This invention includes peptides that contain the minimal binding domain and analogs of these peptides. Another aspect of the invention includes methods of elucidating the minimal ankyrin binding domain(s) of other proteins which interact with ankyrin. Lastly, the invention includes methods of screening for compounds that inhibit or enhance the binding of α-Na,K-ATPase or other ankyrin binding proteins to ankyrin as well as methods of modulating the interaction between ankyrin and proteins which bind to it with said compounds.</p> |
