| pubmed-article:11592056 | pubmed:abstractText | A de novo designed pore-forming small globular protein (SGP) with antitumor activity consists of four helices: 3 basic amphipathic helices composed of Leu and Lys surrounding a central hydrophobic helix composed of oligoalanine. These helices are connected by a beta-turn-forming sequence and two beta-turn-unfavorable ones (S. Lee, T. Kiyota, T. Kunitake, E. Matsumoto, S. Yamashita, K. Anzai, and G. Sugihara Biochemistry 1997, Vol. 36, pp. 3782-3791). In the present work, we designed and synthesized three new SGP analogs in order to study the stoichiometric packing geometry and stability of SGP. The replacement of alanines in the central helix of SGP with leucines (SGP-L), which make the helix much larger in size and more hydrophobic, resulted in an equilibrium of monomeric-trimeric structure. The replacement of some Lys residues by Glu residues in the hydrophilic regions of the amphipathic helices (SGP-E) led to a decrease in helical content and the formation of an equilibrium of monomeric-trimeric structure. The alteration of beta-turn regions with Gly residues, which makes these regions flexible (SGP-G), established an equilibrium of monomeric-dimeric states in buffer. The hydrophobic alpha-helix of SGP-L penetrated into the lipid bilayers in a manner that stabilized model membranes and biomembranes, whereas the central helices of SGP-G and -E destabilized them by forming channels. SGP and its analogs may be a useful model to study the role of the hydrophobic and hydrophilic regions in the formation of monomer-oligomer of proteins and to better understand the insertion of membrane targeting proteins into biomembranes. | lld:pubmed |
