TipA, a Bdellovibrio bacteriovorus BPI-like double-TULIP is opened by its adapter protein, TipB

Bdellovibrio bacteriovorus is a predatory bacterium that invades the periplasm of other Gram-negative bacteria and liberates prey biomolecules for replication. Bdellovibrio has a wealth of genes that encode unique proteins to enable this lifestyle. Using a series of x-ray structures, we show that the operonal pairing of bd2538 and bd2539, encode a double T ULIP (tubular lipid binding protein) invasion p rotein A (TipA) and a small beta sandwich (TipB), respectively. TipA has a specialised N-terminal TULIP domain with a beta hairpin and helix that mediate homodimerisation through hairpin interdigitation. This dimerisation creates a large, continuous, enclosed lumen that we demonstrate to contain multiple lipid molecules. In addition, we show that TipB functions as a small adapter protein that binds to TipA using specialised loops that bury into the TipA hydrophobic core. This binding forms a clamp on the edge of the N-terminal beta sheet and induces a large 20 Å conformational change, opening the TULIP fold to create an accessible interior. This study presents the first structural characterisation of lipid binding proteins in Bdellovibrio , and the first example of conformational change in TULIPs mediated by an adaptor protein.