Evidence map›Paper›PMID 20585582›Full record

ArticlePloS one2010

The minimal autoinhibited unit of the guanine nucleotide exchange factor intersectin.

K Farid Ahmad, Wendell A Lim

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.8field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Small molecule targeting Cdc42-intersectin interaction disrupts Golgi organization and suppresses cell motility.Proceedings of the National Academy of Sciences of the United States of America · 2013
    Article
  12. Article
  13. Structure of the Rho-specific guanine nucleotide-exchange factor Xpln.Acta crystallographica. Section F, Structural biology and crystallization communications · 2012
    Article
  14. Review
  15. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

K Farid AhmadDepartment of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, California, United States of America.
Wendell A Lim
University of California, San Francisco · US

Funding

PROTEIN RECOGNITION IN SIGNAL TRANSDUCTIONR01GM055040 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIM, WENDELL A · 1997 to 2015
$3.5M
PROTEIN INTERACTIONS REGULATING CELL MOTILITYR01GM062583 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIM, WENDELL A · 2001 to 2009
$2.2M
CIHRHoward Hughes Medical InstituteNIGMS NIH HHS R01 GM055040NIGMS NIH HHS R01-GM055040NIGMS NIH HHS R01 GM062583NIGMS NIH HHS R01-GM062583
6 · The paper itself

Abstract

Intersectin-1L is a member of the Dbl homology (DH) domain guanine nucleotide exchange factors (GEF) which control Rho-family GTPase signaling. Intersectin-1L is a GEF that is specific for Cdc42. It plays an important role in endocytosis, and is regulated by several partners including the actin regulator N-WASP. Intact intersectin-1L shows low Cdc42 exchange activity, although the isolated catalytic DH domain shows high activity. This finding suggests that the molecule is autoinhibited. To investigate the mechanism of autoinhibition we have constructed a series of domain deletions. We find that the five SH3 domains of intersectin are important for autoinhibition, with the fifth domain (SH3(E)) being sufficient for the bulk of the autoinhibitory effect. This SH3 domain appears to primarily interact with the DH domain. We have determined the crystal structure of the SH3(E)-DH domain construct, which shows a domain swapped arrangement in which the SH3 from one monomer interacts with the DH domain of the other monomer. Analytical ultracentrifugation and gel filtration, however, show that under biochemical concentrations, the construct is fully monomeric. Thus we propose that the actual autoinhibited structure contains the related intramolecular SH3(E)-DH interaction. We propose a model in which this intramolecular interaction may block or distort the GTPase binding region of the DH domain.

Indexed as

Adaptor Proteins, Vesicular TransportAmino Acid SequenceAnimalsCatalytic DomainCrystallography, X-RayGuanine Nucleotide Exchange FactorsMiceModels, MolecularMolecular Sequence DataProtein Structure, SecondarySequence Homology, Amino AcidAdaptor Proteins, Vesicular TransportGuanine Nucleotide Exchange Factorsintersectin 1

Identifiers

PMID20585582
PMCPMC2892021
OpenAlexW2080874788

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.