The RalB-RLIP76 Complex Reveals a Novel Mode of Ral-Effector Interaction

RLIP76 (RalBP1) is a multidomain protein that interacts with multiple small G protein families: Ral via a specific binding domain, and Rho and R-Ras via a GTPase activating domain. RLIP76 interacts with endocytosis proteins and has also been shown to behave as a membrane ATPase that transports chemo...

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Bibliographic Details
Published in:Structure (London) 2010-08, Vol.18 (8), p.985-995
Main Authors: Fenwick, R. Brynmor, Campbell, Louise J., Rajasekar, Karthik, Prasannan, Sunil, Nietlispach, Daniel, Camonis, Jacques, Owen, Darerca, Mott, Helen R.
Format: Article
Language:English
Subjects:
Affinity
Amino Acid Sequence
ATP-Binding Cassette Transporters - chemistry
ATP-Binding Cassette Transporters - metabolism
Binding
CELLBIO
Coiling
Crystallography, X-Ray
GTPase-Activating Proteins - chemistry
GTPase-Activating Proteins - metabolism
Humans
In vitro testing
Membranes
Models, Molecular
Molecular Sequence Data
Molecular Structure
Multiprotein Complexes - chemistry
Multiprotein Complexes - metabolism
Nuclear Magnetic Resonance, Biomolecular
Protein Binding
Protein Conformation
Proteins
ral GTP-Binding Proteins - chemistry
ral GTP-Binding Proteins - metabolism
Residues
Scintillation Counting
Sequence Alignment
SIGNALING
Transport
Vesicular Transport Proteins - metabolism
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Description
Summary:RLIP76 (RalBP1) is a multidomain protein that interacts with multiple small G protein families: Ral via a specific binding domain, and Rho and R-Ras via a GTPase activating domain. RLIP76 interacts with endocytosis proteins and has also been shown to behave as a membrane ATPase that transports chemotherapeutic agents from the cell. We have determined the structure of the Ral-binding domain of RLIP76 and show that it comprises a coiled-coil motif. The structure of the RLIP76-RalB complex reveals a novel mode of binding compared to the structures of RalA complexed with the exocyst components Sec5 and Exo84. RLIP76 interacts with both nucleotide-sensitive regions of RalB, and key residues in the interface have been identified using affinity measurements of RalB mutants. Sec5, Exo84, and RLIP76 bind Ral proteins competitively and with similar affinities in vitro. [Display omitted] ► The Ra1 binding coiled coil is the first structure available of RLIP/Ra1BP1 ► RLIP76 interacts with the switch regions of Ra1B using a novel Ra1-binging motif ► The binding to Ra1B is different from, and competitive with, exocyst component binding ► Mutational analysis shows that RLIP76 Trp-430 is a hotspot in the interface
ISSN:0969-2126
1878-4186
DOI:10.1016/j.str.2010.05.013