The exercises of de novo protein design have shown that a unique structure is very difficult to attain. As the determinants of structural uniqueness in native proteins, we propose a negative factor, namely, the decrease in the side-chain conformational entropy, which can suppress the structural diversity, and can destabilize the intermediate folding state. A small globular protein, c-Myb R3, includes Ile residues on each of the three helices, respectively. These Ile residues were changed to Leu residues, to investigate the role of a β-branched amino acid in an α-helix for structural uniqueness.
Lanthanoides are known to affect a variety of membrane phenomena; for example, an inhibition of voltage-dependent Ca2+ channels. Recent studies have revealed that each of aminoacid receptor-channels is affected in its activation by La3+ in a different manner. La3+ inhibits kainate and NMDA receptor-channel responses while potentiating AMPA, GABAA, GABAC and glycine receptor-channel responses. A positive modulation by La3+ of GABAA receptorchannels on rat septal cholinergic neurons in culture is shared by other lanthanoide ions and Y3+ but not by Sc3+, all of which belong to the same group (III a) in the periodic table. It is suggested that there may be a specific site for binding of lanthanoides on GABAA receptorchannels.
Both SecA and SecG, components of the protein translocation machinery of E. coli, were found to undergo significant structure changes during protein translocation. SecA repeats the cycle of membrane-insertion and deinsertion while SecG repeats the cycle of membrane topology inversion. Molecular mechanisms whereby the structure changes of SecA and SecG drive protein translocation are discussed.
Essential ideas in the protein 3D-1D compatibility analysis are briefly introduced. The 3D-1D alignment was revolutionary in the establishment of the methodology. The method is applicable for structure prediction, stability evaluation of point mutants, deducing functional sites etc. In these applications it appears free of the protein folding problem, however, this is not the case if we try to design de-novo sequence.