Structure of tuberoinfundibular peptide of 39 residues

The recently identified natural peptide ligand, tuberoinfundibular peptide of 39 residues (TIP39) for the parathyroid hormone-2 (PTHS) receptor has be en structurally characterized by high resolution NMR, circular dichroism, a nd computer simulations. The structural features of TIP39, determined in th e presence of a zwitterionic lipid to mimic the membrane environment of the G-protein-coupled PTH2 receptor, consist of two a-helices, Ala(5)-Arg(21) and Leu(26)-Val(35). Although TIP39 shares limited sequence homology with p arathyroid hormone (PTH), a comparison of the structural features of TIP39 and PTH illustrates a similar topological display of residues of the N-term inal helix important for PTH2 receptor activation. The C-terminal helix of TIP39 differs from that of PTH with respect to size and amphipathicity, sug gesting an altered mode of binding for TIP39, consistent with the receptor chimera and ligand truncation studies presented in the accompanying paper ( Hoare, S. R. J., Clark, J, A, and Usdin, T. B. (2000) J. Biol. Chen. 275, 2 7274-27283). The structural characterization of TIP39 also provides some in sight into the lack of affinity of this novel ligand for the PTH1 receptor.