Exo84 and Sec5 are competitive regulatory Sec6/8 effectors to the RalA GTPase
Open accessAbstract
The Sec6/8 complex, also known as the exocyst complex, is an octameric protein complex that has been implicated in tethering of secretory vesicles to specific regions on the plasma membrane. Two subunits of the Sec6/8 complex, Exo84 and Sec5, have recently been shown to be effector targets for active Ral GTPases. However, the mechanism by which Ral proteins regulate the Sec6/8 activities remains unclear. Here, we present the crystal structure of the Ral-binding domain of Exo84 in complex with active RalA. The structure reveals that the Exo84 Ral-binding domain adopts a pleckstrin homology domain fold, and that RalA interacts with Exo84 via an extended interface that includes both switch regions. Key residues of Exo84 and RalA were found that determine the specificity of the complex interactions; these interactions were confirmed by mutagenesis binding studies. Structural and biochemical data show that Exo84 and Sec5 competitively bind to active RalA. Taken together, these results further strengthen the proposed role of RalA-regulated assembly of the Sec6/8 complex.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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 [9]
The section “Exo84 and Sec5 competitively bind to RalA in vitro” (page unavailable) shows that two exocyst subunits have overlapping binding sites on active RalA and compete with each other. It does not establish that Ralbp1 shares that site or that exocyst binding causes Ralbp1 to dissociate. (LLM, conf=0.82)
Experimental — accuracy not yet measuredRalA is a vesicle-bound small GTPase promoting exocytosis through interacting with the exocyst complex.
“Reps1 and Ralbp1 form a binary complex that recognizes RalA, a vesicle-bound small guanosine triphosphatases (GTPase) promoting exocytosis through interacting with the exocyst complex.”
From Regulation of cargo exocytosis by a Reps1-Ralbp1-RalA module (2023) · cites this paper as [9]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cited by
Sorted by citations
M-Sec promotes membrane nanotube formation by interacting with Ral and the exocyst complex
Hase, K., Kimura, S., Takatsu, H., Ohmae, M., Kawano, S., Kitamura, H., Ito, M., Watarai, H., Hazelett, C. C., Yeaman, C., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1990 · Cited by 402 · see citing works
Cryo-EM structure of the exocyst complex
Mei, K., Li, Y., Wang, S., Shao, G., Wang, J., Ding, Y., Luo, G., Yue, P., Liu, J.-J., Wang, X., et al. (2018) · Nature Structural & Molecular Biology · doi:10.1038/s41594-017-0016-2 · Cited by 156 · see citing works
Discovery and characterization of small molecules that target the GTPase Ral
Yan, C., Liu, D., Li, L., Wempe, M. F., Guin, S., Khanna, M., Meier, J., Hoffman, B., Owens, C., Wysoczynski, C. L., et al. (2014) · Nature · doi:10.1038/nature13713 · Cited by 150 · see citing works
Ral mediates activity‐dependent growth of postsynaptic membranes via recruitment of the exocyst
Teodoro, R. O., Pekkurnaz, G., Nasser, A., Higashi‐Kovtun, M. E., Balakireva, M., McLachlan, I. G., Camonis, J., & Schwarz, T. L. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.147 · Cited by 61 · see citing works
Ral GTPase and the exocyst regulate autophagy in a tissue‐specific manner
Tracy, K., Velentzas, P. D., & Baehrecke, E. H. (2016) · The EMBO Reports · doi:10.15252/embr.201541283 · Cited by 22 · see citing works
Regulation of cargo exocytosis by a Reps1-Ralbp1-RalA module
Wang, S., Chen, X., Crisman, L., Dou, X., Winborn, C. S., Wan, C., Puscher, H., Yin, Q., Kennedy, M. J., & Shen, J. (2023) · Science Advances · doi:10.1126/sciadv.ade2540 · Cited by 14 · see citing works
- Authors
- Jin, R., Junutula, J. R., Matern, H. T., Ervin, K. E., Scheller, R. H., & Brunger, A. T.
- Affiliations
- Howard Hughes Medical Institute (US)
- Genentech (US)
- Venue
- The EMBO Journal
- Published
- 2005-05-26
- Volume
- 24
- Issue
- 12
- Pages
- 2064-2074
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1150893
- OpenAlex
- W2063063619
- Cited by
- 145
- References
- 0
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 2 · 2020: 8 · 2019: 4 · 2018: 7 · 2017: 9 · 2016: 5 · 2015: 10 · 2014: 7 · 2013: 9 · 2012: 12
- FWCI
- 3.30
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences
- Basic Energy Sciences
- Biological and Environmental Research
- 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 › Extracellular vesicles in disease
- Keywords
- Sec5, exocyst, pleckstrin homology domain, competitive binding, protein complex formation, crystal structure
- MeSH terms
- Amino Acid Sequence, Animals, Carrier Proteins, Guanosine Triphosphate, Humans, Membrane Proteins, Molecular Sequence Data, Protein Binding, Protein Structure, Secondary, Protein Structure, Tertiary, ral GTP-Binding Proteins, Vesicular Transport Proteins, Mice, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
