Solution Structure of a Calmodulin-Binding Domain in the Carboxy-Terminal Region of HIV Type 1 gp160

ABSTRACT The cytosolic domain of human immunodeficiency virus gp160 glycoprotein contains two calmodulin-binding regions. The role of these domains in modulating intracellular calmodulin signaling is of considerable interest in unraveling the mechanism whereby calmodulin regulates Fas-mediated apoptosis in HIV-infected cells. In this investigation we have employed 2D-NMR spectroscopy to determine the solution structure of the 30-residue calmodulin-binding domain corresponding to residues 826–855 of gp160. In solution, the gp160 (826–855) peptide exhibits a high degree of segmental flexibility. Within its conformational manifold, we have detected two separate flexible amphipathic helices involving residues 826–841 and 846–855 connected by a highly flexible type-II β-turn at Pro-843 and Arg-844. The observed NOE pattern as well as the observation of long-range NOE contacts between the side chains of His-841 and Ile-846 are compatible with the presence of this turn in the conformational manifold of this pept...