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Protein LidA from Legionella is a Rab GTPase supereffector

2011; National Academy of Sciences; Volume: 108; Issue: 44 Linguagem: Inglês

10.1073/pnas.1113133108

1091-6490

Stefan Schoebel, Adam Cichy, Roger S. Goody, Aymelt Itzen,

Cellular transport and secretion

The causative agent of Legionnaires disease, Legionella pneumophila , injects several hundred proteins into the cell it infects, many of which interfere with or exploit vesicular transport processes. One of these proteins, LidA, has been described as a Rab effector (i.e., a molecule that interacts preferentially with the GTP-bound form of Rab). We describe here the structure and biochemistry of a complex between the Rab-binding domain of LidA and active Rab8a. LidA displays structural peculiarities in binding to Rab8a, forming a considerably extended interface in comparison to known mammalian Rab effectors, and involving regions of the GTPase that are not seen in other Rab:effector complexes. In keeping with this extended binding interface, which involves four α-helices and two pillar-like structures of LidA, the stability of LidA-Rab interactions is dramatically greater than for other such complexes. For Rab1b and Rab8a, these affinities are extraordinarily high, but for the more weakly bound Rab6a, K d values of 4 nM for the inactive and 30 pM for the active form were found. Rab1b and Rab8a appear to bind LidA with K d values in the low picomolar range, making LidA a Rab supereffector.