Structural Insights into the Regulation of Foreign Genes in Salmonella by the Hha/H-NS Complex

A Three-protein Charge Zipper Stabilizes a Complex Modulating Bacterial Gene Silencing

“…Our solution structural model of the Hha⅐H-NS complex can be compared with the recently published crystal structure of an equivalent complex (21). Despite the fact that the crystal structure has missing electron density for atoms in 50 side chains, including most of the interface region, the x-ray and NMR models have very similar backbone structures.…”

“…However, because of the electrostatic asymmetry of Hha itself, a new positively charged patch (from Hha) is displayed (19,20), although at a different position with respect to the H-NS oligomer axis. The presence of Hha-like proteins is believed to change the "matching condition" between DNA binding and H-NS oligomerization and, therefore, the DNA silencing specificity (20,21,50). Mutagenesis in the positively charged region of Hha clearly demonstrates that this region is critical for transcriptional repression but not for H-NS binding (21,24).…”

“…The presence of Hha-like proteins is believed to change the "matching condition" between DNA binding and H-NS oligomerization and, therefore, the DNA silencing specificity (20,21,50). Mutagenesis in the positively charged region of Hha clearly demonstrates that this region is critical for transcriptional repression but not for H-NS binding (21,24).…”

“…We suggest at least three possible effects. (a) Due to its positively charged surface, a direct interaction between Hha and DNA was suggested (21). The existence of pervasive motions in the free molecule would increase the entropic penalty upon binding and may decrease spurious binding of Hha to DNA.…”

“…A detailed analysis of the structures of the Hha⅐H-NS complex in crystals (21) and in solution (first reported here) unraveled a charge zipper with conserved residues contributed by three proteins (Hha/YmoA and the two units of an antiparallel H-NS dimer). This feature explains the high selectivity of the Hha/YmoA interaction with H-NS.…”