Evidence map›Paper›PMID 34739841›Full record

ArticleStructure (London, England : 1993)2022

Crystal structure of the Tspan15 LEL domain reveals a conserved ADAM10 binding site.

Colin H Lipper, Khal-Hentz Gabriel, Tom C M Seegar, Katharina L Dürr, Michael G Tomlinson, Stephen C Blacklow

Open access · greenAbstract read
In one paragraph

Article in Structure (London, England : 1993), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

14 citing papers in PubMed, 24 citations in OpenAlex.

  1. Lipid-Facilitated Opening of the ADAM10 Sheddase Revealed by Enhanced Sampling Simulations.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  2. Article
  3. Tetraspanin TSP-12 and SUP-17/ADAM10 exhibit cell type-specific codependence for trafficking through the Golgi.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. ADAM10-a "multitasker" in sepsis: focus on its posttranslational target.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023
    Review
  14. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 4 institutions in 2 countries.

Colin H LipperDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Khal-Hentz GabrielDepartment of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02215, USA.
Tom C M SeegarUniversity of Cincinnati School of Medicine, Department of Molecular Genetics, Biochemistry, and Microbiology, Cincinnati, OH 45267, USA.
Katharina L DürrOMass Therapeutics, Oxford OX4 4GE, UK.
Michael G TomlinsonSchool of Biosciences, University of Birmingham, Birmingham B15 2TT, UK.
Stephen C BlacklowDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02215, USA. Electronic address: stephen_blacklow@hms.harvard.edu.
Harvard University · USDana-Farber Cancer Institute · USUniversity of Birmingham · GBUniversity of Cincinnati · US

Funding

Overall EvaluationP41GM103403 · NIGMS · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2012 to 2017
$14.3M
Notch Signaling in CancerR35CA220340 · NCI · HARVARD MEDICAL SCHOOL · PI BLACKLOW, STEPHEN C. · 2017 to 2023
$7.1M
Structure and Regulation of Ectodomain Sheddases in Development and DiseaseR35GM146830 · NIGMS · UNIVERSITY OF CINCINNATI · PI Tom C M Seegar · 2022 to 2026
$2.2M
Biotechnology and Biological Sciences Research Council BB/P00783X/1NCI NIH HHS R35 CA220340NIGMS NIH HHS P41 GM103403NIGMS NIH HHS R35 GM146830
6 · The paper itself

Abstract

Tetraspanins are four-pass transmembrane proteins that function by regulating trafficking of partner proteins and organizing signaling complexes in the membrane. Tspan15, one of a six-member TspanC8 subfamily, forms a complex that regulates the trafficking, maturation, and substrate selectivity of the transmembrane protease ADAM10, an essential enzyme in mammalian physiology that cleaves a wide variety of membrane-anchored substrates, including Notch receptors, amyloid precursor protein, cadherins, and growth factors. We present here crystal structures of the Tspan15 large extracellular loop (LEL) required for functional association with ADAM10 both in isolation and in complex with the Fab fragment of an anti-Tspan15 antibody. Comparison of the Tspan15 LEL with other tetraspanin LEL structures shows that a core helical framework buttresses a variable region that structurally diverges among LELs. Using co-immunoprecipitation and a cellular N-cadherin cleavage assay, we identify a site on Tspan15 required for both ADAM10 binding and promoting substrate cleavage.

Indexed as

MutationADAM10 ProteinAmyloid Precursor Protein SecretasesAntigens, CDBinding SitesCadherinsCell LineCrystallography, X-RayGene Knockout TechniquesHumansMembrane ProteinsModels, MolecularProtein BindingProtein Structure, SecondaryTetraspaninsADAM10 ProteinADAM10 protein, humanAmyloid Precursor Protein SecretasesAntigens, CDCadherinsCDH2 protein, humanMembrane ProteinsTetraspaninsTSPAN15 protein, humancell adhesionN-cadherinNotch signalingproteolysistetraspaninX-ray crystallography

Identifiers

PMID34739841
PMCPMC8818019
OpenAlexW3210968293

What OpenQuestion holds

Textmetadata
LicenceTDM
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.