Protein LidA from Legionella is a Rab GTPase supereffector
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Protein LidA from Legionella is a Rab GTPase supereffector. / Schoebel, Stefan; Cichy, Adam L; Goody, Roger S; Itzen, Aymelt.
in: P NATL ACAD SCI USA, Jahrgang 108, Nr. 44, 01.11.2011, S. 17945-50.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -