Protein LidA from Legionella is a Rab GTPase supereffector

TY - JOUR

T1 - Protein LidA from Legionella is a Rab GTPase supereffector

AU - Schoebel, Stefan

AU - Cichy, Adam L

AU - Goody, Roger S

AU - Itzen, Aymelt

PY - 2011/11/1

Y1 - 2011/11/1

N2 - 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.

AB - 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.

KW - Adenosine Monophosphate

KW - Amino Acid Sequence

KW - Bacterial Proteins

KW - Kinetics

KW - Legionella

KW - Models, Molecular

KW - Molecular Sequence Data

KW - rab GTP-Binding Proteins

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1073/pnas.1113133108

DO - 10.1073/pnas.1113133108

M3 - SCORING: Journal article

C2 - 22011575

VL - 108

SP - 17945

EP - 17950

JO - P NATL ACAD SCI USA

JF - P NATL ACAD SCI USA

SN - 0027-8424

IS - 44

ER -