What can we learn from incorrect AlphaFold2 models? (the case of signal transduction)

Stanislaw Dunin-Horkawicz

/Tübingen [DE]

Prokaryotic signal transduction proteins are based on a fibrous coiled-coil backbone in which functional domains can be identified. These domains are specialized for functions such as signal recognition, transduction across the membrane, modulation, and initiation of downstream effects. Experimental structures of these domains have been essential for exploring hypotheses about signaling mechanisms, underscoring the potential of AlphaFold2 to further our understanding. In this work, we applied AlphaFold2 to a peculiar family of signaling proteins that contain long arrays of signal modulation domains (HAMPs), which typically occur in a single copy in canonical signal transduction proteins. Our results suggest that the function of these proteins may depend on the intrinsic conflict between the conformations of adjacent HAMP domains, while also highlighting the applicability of AlphaFold2 to the study of dynamic proteins.

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