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Cited by 46Cellular transport and secretionProtein Kinase Regulation and GTPase SignalingReceptor Mechanisms and Signaling

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

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Fenwick, R. Brynmor, Campbell, Louise J., Rajasekar, Karthik, Prasannan, Sunil, Nietlispach, Daniel, Camonis, Jacques, Owen, Darerca, Mott, Helen R.·2010·Structure
DOI 10.1016/j.str.2010.05.013PMC PMC4214634
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Abstract

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.

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  • Ralbp1 selectively binds to the active GTP-bound form of Ral GTPases.

    “Ralbp1 selectively binds to the active GTP-bound form of Ral GTPases, offering a reliable approach to quantify active RalA proteins (37, 45, 46).”

    From Regulation of cargo exocytosis by a Reps1-Ralbp1-RalA module (2023) · cites this paper as [45]

    In Results and Discussion, the paper reports high-affinity binding of RLIP76 to RalB·GTP and shows that its binding domain contacts nucleotide-sensitive switch regions of RalB. The passages do not establish selective binding over GDP-bound Ral or demonstrate that selectivity across Ral GTPases. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Ralbp1 interacts with switches 1 and 2 of GTP-bound Rals, the same region recognized by RalGAPs.

    “Ralbp1 interacts with switches 1 and 2 of GTP-bound Rals, the same region recognized by RalGAPs (12, 45, 60).”

    From Regulation of cargo exocytosis by a Reps1-Ralbp1-RalA module (2023) · cites this paper as [45]

    The Results and Discussion section (“Structure of the RLIP76 GBD-RalB complex”; page unavailable) shows that RLIP76/RalBP1 contacts switches 1 and 2 of activated RalB. The paper does not establish that RalGAPs recognize the same region; its discussion of GAP activity concerns RLIP76 acting on Rac1 and Cdc42, not RalGAP binding to Ral. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Subsequent dissociation of Ralbp1 from RalA is expected to result from direct competition from exocyst as Ralbp1 and exocyst recognize the same domain of GTP-bound Ral GTPases.

    “Subsequent dissociation of Ralbp1 from RalA, on the other hand, is expected to result from direct competition from exocyst as Ralbp1 and exocyst recognize the same domain of GTP-bound Ral GTPases (4, 9, 45).”

    From Regulation of cargo exocytosis by a Reps1-Ralbp1-RalA module (2023) · cites this paper as [45]

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Research works printed but not linked: 45

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Authors
Fenwick, R. B., Campbell, L. J., Rajasekar, K., Prasannan, S., Nietlispach, D., Camonis, J., Owen, D., & Mott, H. R.
Affiliations
  • University of Cambridge (GB)
  • Institut Curie (FR)
Corresponding author
  • Owen, Darerca
  • Mott, Helen R.
ORCID
Venue
Structure
Publisher
Elsevier BV
Published
2010-08
Volume
18
Issue
8
Pages
985-995
ISSN
0969-2126 (ISSN-L)
DOI
10.1016/j.str.2010.05.013
PMC
PMC4214634
OpenAlex
W2161723168
Cited by
46
References
0
Citations by year
2026: 2 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 5 · 2019: 4 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 3 · 2014: 4 · 2013: 6 · 2012: 1
FWCI
1.70
Type
journal article
Language
en
Open access
Licence
Locations
  • Structure (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Wellcome Trust (094234)
  • Cancer Research UK (C9467/A4658)
  • Agence Nationale de la Recherche (ANR-08-BLAN-0290)
  • Biotechnology and Biological Sciences Research Council (BB/E013228/1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
RLIP76, RALBP1, RalB, coiled-coil domain, protein complex structure, competitive binding, Sec5, exocyst, endocytosis
MeSH terms
Amino Acid Sequence, Humans, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Conformation, Scintillation Counting, Molecular Structure, Sequence Alignment, Crystallography, X-Ray, ATP-Binding Cassette Transporters, Nuclear Magnetic Resonance, Biomolecular, GTPase-Activating Proteins, ral GTP-Binding Proteins, Vesicular Transport Proteins, Multiprotein Complexes

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