WMS Events Calendar

Abstract: Protein-protein interactions are crucial for carrying out biological functions and for regulating activities. I will be presenting two stories in this direction: membrane-bound channels and the actin-tropomyosin matrix proteins. Gap junction proteins orchestrate across cells to form channels that permit cytosolic molecules such as glutamate and ATP to leak into the extracellular medium. Innexins in worms and connexins in eukaryotes belong to this superfamily to perform these functions. Interestingly, despite their functional similarities, their oligomeric states are different. Innexins form octamers, while connexins for hexamers. Pannexins are intermediate sequences which form only heptameric hemichannels, but not functional channels. We asked a general question about the oligomeric preferences of the superfamily members by simply threading the alternate quaternary states and compared the interface psuedoenergies through an in-house algorithm called PPCheck (Sukhwal and Sowdhamini, 2015). There are various isomers of these proteins and we also examined few combinations of oligomers through modelling approaches. Results indicate that considerable specificity is achieved through N-terminal loop regions and hemi-channel interfaces.

Actin-tropomyosin interactions are crucial for biological processes such as muscle contraction including cardiac muscles. Whereas the coiled-coil of human tropomyosin, TPM1, interacts with seven molecules of actin, all along its periods of heptad repeats, we examined shorter length tropomyosins (such as TPM4 and yeast homologue which binds to only four actins) through successive docking and energy calculations to compare the actin-tropomyosin interface. I will discuss the results which indicate shorter length tropomyosins bind more strongly at the heptads. These might be compensatory mechanisms to combat the length differences. It will be interesting to follow on biophysical validations and the functional basis of length variations amongst homologous proteins.