Structure of the GTPase-binding Domain of Sec5 and Elucidation of its Ral Binding Site
Open accessAbstract
The exocyst complex is involved in the final stages of exocytosis, when vesicles are targeted to the plasma membrane and dock. The regulation of exocytosis is vital for a number of processes, for example, cell polarity, embryogenesis, and neuronal growth formation. Regulation of the exocyst complex in mammals was recently shown to be dependent upon binding of the small G protein, Ral, to Sec5, a central component of the exocyst. This interaction is thought to be necessary for anchoring the exocyst to secretory vesicles. We have determined the structure of the Ral-binding domain of Sec5 and shown that it adopts a fold that has not been observed in a G protein effector before. This fold belongs to the immunoglobulin superfamily in a subclass known as IPT domains. We have mapped the Ral binding site on this domain and found that it overlaps with protein-protein interaction sites on other IPT domains but that it is completely different from the G protein-geranyl-geranyl interaction face of the Ig-like domain of the Rho guanine nucleotide dissociation inhibitor. This mapping, along with available site-directed mutagenesis data, allows us to predict how Ral and Sec5 may interact.
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?
The interaction of RalA with Sec5 and Exo84 is thought to promote complex assembly, vesicle exocytosis, and membrane addition.
“this interaction is thought to promote complex assembly, vesicle exocytosis, and membrane addition (Moskalenko et al, 2002(Moskalenko et al, , 2003;;Sugihara et al, 2002;Fukai et al, 2003;Mott et al, 2003;Wang et al, 2004;Jin et al, 2005;Hase et al, 2009).”
From Ral mediates activity‐dependent growth of postsynaptic membranes via recruitment of the exocyst (2013) · cites this paper as Mott et al, 2003
The Abstract (page not provided) says Ral binds Sec5 and that this interaction is thought necessary to anchor the exocyst to secretory vesicles; it also links Ral to regulation of exocytosis. The concluding passage (page not provided) proposes studying the interaction’s role in exocyst assembly, but does not establish that it promotes assembly. Our copy lists Exo84 as an exocyst component without saying it binds RalA, and does not attribute membrane addition to the RalA–Sec5 interaction. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Structure of the DNA-binding domains from NFAT, Fos and Jun bound specifically to DNA
Chen, L., Glover, J. N. M., Hogan, P. G., Rao, A., & Harrison, S. C. (1998) · Nature · doi:10.1038/32100 · Cited by 521 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- Matern, H. T., Yeaman, C., Nelson, W. J., and Scheller, R. H. (2001) Proc. Natl. Acad. Sci. U. S. A. 98, 9648 -9653
- Luo, J. Q., Liu, X., Frankel, P., Rotunda, T., Ramos, M., Flom, J., Jiang, H., Feig, L. A., Morris, A. J., Kahn, R. A., and Foster, D. A. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 3632-3637
- Bork, P., Doerks, T., Springer, T. A., and Snel, B. (1999) Trends Biochem. Sci. 24, 261-263
Cited by
Sorted by citations
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
Self-citationSiponen, M. I., Wisniewska, M., Lehtiö, L., Johansson, I., Svensson, L., Raszewski, G., Nilsson, L., Sigvardsson, M., & Berglund, H. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.c110.150482 · Cited by 34 · see citing works
- Authors
- Mott, H. R., Nietlispach, D., Hopkins, L. J., Mirey, G., Camonis, J. H., & Owen, D.
- Affiliations
- University of Cambridge (GB)
- Toxicologie Alimentaire (FR)
- Institut Curie (FR)
- Corresponding author
- Mott, Helen R.
- Owen, Darerca
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-05
- Volume
- 278
- Issue
- 19
- Pages
- 17053-17059
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2058489078
- Cited by
- 39
- References
- 1
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2021: 1 · 2020: 1 · 2018: 1 · 2016: 2 · 2015: 4 · 2014: 4 · 2013: 2 · 2012: 3
- FWCI
- 0.68
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Funders
- Wellcome Trust
- Cancer Research UK
- European Commission
- Directorate for Biological Sciences
- Medical Research Council
- Biotechnology and Biological Sciences Research Council
- 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 complex, Ral, immunoglobulin superfamily, GTPase-binding domain, exocytosis, vesicle docking, protein-protein interaction, RhoGDI, geranylgeranylation, protein structure
- MeSH terms
- Amino Acid Sequence, Animals, Binding Sites, Escherichia coli, Membrane Proteins, Molecular Sequence Data, Protein Binding, Protein Conformation, Sequence Alignment, Protein Structure, Tertiary, GTP Phosphohydrolases, ral GTP-Binding Proteins, Vesicular Transport Proteins, Mice
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
