Congratulations to our grad student Nuo Tian for a successful defense of her Master’s thesis on Jan 12, 2021.  The title of her thesis is “Structural and evolutionary relationships within the ATP-binding cassette (ABC) superfamily”.


ATP-binding Cassette (ABC) transporters use ATP as an energy source and move a variety of substrates across cellular membranes. Previous studies based on primary protein sequence data suggested that integral membrane ABC exporters evolved independently at least three times, giving rise to three ABC types. Given the increasing availability of ABC structures in the Protein Data Bank (PDB) and the significantly larger number of primary sequences, we are now able to investigate whether the most current data support the conclusions obtained based on sequence analyses alone. We conducted sequence and structural analyses on the transmembrane and ATPase domains of the three ABC types, which involved independent clustering analyses of protein sequences and 3D structural similarities. Our clustering of both the transmembranal and the ATPase domains show that ABC1 forms a monophyletic group, whereas ABC2 and ABC3 share a major branch. The topology similarity between trees constructed based on the two domains strongly supports the notion that these two domains have co-evolved. Our analysis of repeat units did not produce conclusive evidence supporting the observed TMS topologies for ABC1 (2+2+2) and ABC2 (3+3). However, taking into consideration that the length of the loops connecting TMSs is well conserved within each ABC type, and the major role that loops play on shaping repeat units, we postulate that the previously published topologies are correct. Our results provide insights into the evolutionary relationships between ABC types and serve as a guide for future studies of the ABC superfamily.