These residues participate in hydrophobic interactions that contribute to stabilizing the helical Y-27632 dihydrochloride bundle by forming an extended hydrophobic platform along the helix axis. These interactions include the aromatic-aromatic contacts between F60 and F64 in an edge-to-face fashion, and many aromatic-aliphatic and aliphatic-aliphatic contributions. For example, close contacts in the upper part of the bundle involve the aromatic rings of F60 and F64 with the aliphatic chains of V61, L94, L97, I98, V102, L105, A116, and L117 . In the lower part of the bundle, interactions involve V71, L74, L75, A87, A88, L91, L94, L120, A123, L124 also from the three helices . At the bottom A78, V81, L84, L131 belong to loop 2 and the N- and C-termini of helices a3 and a4, respectively . Close to the disordered part, the aromatic rings of F103 and F104 interact with the methyl groups of V102, L105 and A106, all located in loop 3 . Y108 is also close to A106 . In contrast to hydrophobic interactions, electrostatic interactions are much less abundant. A salt bridge connecting the side-chains of E67 and R90, that links helices a2 and a3 , is present. The side chains of residue pairs E76-R127, E79-R83, E82-R83, E126- R127, and E126-R129 are relatively close to each other and may form favourable charge-charge interactions. The surface of the TBCC N-terminal domain is highly charged . Interestingly, two contiguous regions differing in 90u rotation concentrate longitudinally charges of opposite signs while on the two remaining faces there is a more random distribution. Such a distribution would favour protein-protein interactions with partners having the appropriate charge complementarities. Also, remarkably, the 30-residue N-terminal region is very rich in positive charges, except for a central patch of negatively charged residues . The 30-residue N-terminal region concentrates 80% of charged and polar residues with ASAs$30% and these features are likely to be important for the interaction with tubulin as discussed below. We tested whether the TBCC N-terminal domain is able to interact directly with ab-tubulin heterodimer and with two peptides of 16 and 20 residues SB-431542 ALK inhibitor derived from the Cterminus of the b6-tubulin subunit . Region 412�C 431 is highly conserved in tubulins and the last 10�C15 residues of their C-terminus represent the most variable region although it is always negatively charged and contains several Glu residues.