Cellular responses, such as cell fate decision and hormonal regulations, can be regulated by distinct temporal patterns of signaling molecules. However, how temporal patterns of signaling molecules determine the cellular responses remains largely unknown. Recently, we have proposed the concept of “temporal coding”, by which a single molecular species can encode multiple information through its temporal patterns. We found that signaling pathways can process information of stimulation patterns depending on their network motif and kinetics, and cells can regulate downstream molecules depending on stimulation pattern. Thus, “temporal coding” appears to serve as an information-embedding strategy to elicit specific cellular responses.
Protein folding occurs because the native interactions collectively outweigh non-native interactions, resulting in funnel-shaped energy landscapes. The funnel-shaped landscapes of natural proteins are rugged due to evolution for function or neutral drift. We describe an approach to designing ideal protein structures stabilized by consistent local and non-local interactions. The approach is based on rules relating local structures to tertiary motifs, which make possible the design of strongly funneled energy landscapes. Guided by these rules, we succeeded in designing five ideal alpha-beta protein structures with different topologies completely from scratch. These results illuminate how the folding funnels of natural proteins arise.
In mammals, bitter taste is mediated by TAS2Rs, which belong to the large family of seven transmembrane G protein-coupled receptors. Since TAS2Rs are directly involved in the interaction between mammals and their dietary sources, it is likely that these genes evolved to reflect species’ specific diets during mammalian evolution. We have investigated intra- and inter-species differences in the function of TAS2Rs of primates in protein and behavioral levels. The results suggest the common mechanism of the diversification of sensory receptors dependent on the species specific environments.
In a protein environment, proton transfer events can be initiated by configurational changes of pigments (e.g., trans-cis isomerization) or changes in the redox states of cofactors upon photoactivation. These changes lead to alteration of pKa of hydrogen-bond (H-bond) donor and acceptor moieties. In particular, when the pKa values of the two moieties match, a “symmetric H-bond” can be formed. Formation of an unusually short, symmetric H-bond appears to be essential for proton transfer events via H-bonds, and has been observed in photoreceptor proteins.
Selective protein labeling enables us to visualize and engineer proteins in living cells. We developed chemical labeling methods for proteins in test tubes as well as in living cells based on ligand-directed chemistry. Using these methods, small functional molecules can be modified in the vicinity of the ligand binding pocket of target proteins with restoring the protein function. Here we overview our strategies and introduced their applications.