Evidence map›Paper›PMID 40601686›Full record

ArticleeLife2025

Structural insights into heterohexameric assembly of epilepsy-related ligand-receptor complex LGI1-ADAM22.

Takayuki Yamaguchi, Kei Okatsu, Masato Kubota, Ayuka Mitsumori, Atsushi Yamagata, Yuko Fukata, Masaki Fukata, Mikihiro Shibata, Shuya Fukai

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in eLife, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

9 authors.

Takayuki Yamaguchi *Department of Chemistry, Graduate School of Science, Kyoto University, Kyoto, Japan.
Kei Okatsu *Department of Chemistry, Graduate School of Science, Kyoto University, Kyoto, Japan.ORCID https://orcid.org/0000-0001-8949-3750
Masato KubotaDepartment of Chemistry, Graduate School of Science, Kyoto University, Kyoto, Japan.
Ayuka MitsumoriDepartment of Chemistry, Graduate School of Science, Kyoto University, Kyoto, Japan.
Atsushi YamagataLaboratory for Protein Functional and Structural Biology, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.ORCID https://orcid.org/0000-0001-9285-1256
Yuko FukataDivision of Molecular and Cellular Pharmacology, Nagoya University Graduate School of Medicine, Nagoya, Japan.ORCID https://orcid.org/0000-0001-7724-8643
Masaki FukataDivision of Neuropharmacology, Nagoya University Graduate School of Medicine, Nagoya, Japan.ORCID https://orcid.org/0000-0001-5200-9806
Mikihiro ShibataInstitute for Frontier Science Initiative, Kanazawa University, Kanazawa, Japan.ORCID https://orcid.org/0000-0001-5041-3979
Shuya FukaiDepartment of Chemistry, Graduate School of Science, Kyoto University, Kyoto, Japan.ORCID https://orcid.org/0000-0002-1241-1443

Funding

Japan Agency for Medical Research and Development JP24ek0109649Japan Agency for Medical Research and Development JP24wm0625319Japan Society for the Promotion of Science 18H03983Japan Society for the Promotion of Science 19H03162Japan Society for the Promotion of Science 23H00374Japan Society for the Promotion of Science 23H04070Ministry of Education, Culture, Sports, Science and Technology WPI
6 · The paper itself

Abstract

Leucine-rich glioma-inactivated 1 protein (LGI1) is a secreted neuronal protein consisting of the N-terminal leucine-rich repeat (LRR) and C-terminal epitempin-repeat (EPTP) domains. LGI1 is linked to epilepsy, a neurological disorder that can be caused by genetic mutations of genes regulating neuronal excitability (e.g. voltage- or ligand-gated ion channels). ADAM22 is a membrane receptor that binds to LGI1 extracellularly and interacts with AMPA-type glutamate receptors via PSD-95 intracellularly to maintain normal synaptic signal transmission. Structural analysis of the LGI1-ADAM22 complex is important for understanding the molecular mechanism of epileptogenesis and developing new therapies against epilepsy. We previously reported the crystal structure of a 2:2 complex consisting of two molecules of LGI1 and two molecules of the ADAM22 ectodomain (ECD), which is suggested to bridge neurons across the synaptic cleft. On the other hand, multiangle light scattering, small-angle X-ray scattering, and cryo-electron microscopy (cryo-EM) analyses have suggested the existence of a 3:3 complex consisting of three molecules of LGI1 and three molecules of ADAM22. In the previous cryo-EM analysis, many observed particles were in a dissociated state, making it difficult to determine the three-dimensional (3D) structure of the 3:3 complex. In this study, we stabilized the 3:3 LGI1-ADAM22

Indexed as

ADAM ProteinsEpilepsyNerve Tissue ProteinsProtein MultimerizationProteinsAnimalsCryoelectron MicroscopyHumansIntracellular Signaling Peptides and ProteinsModels, MolecularProtein BindingProtein ConformationADAM22 protein, humanADAM ProteinsIntracellular Signaling Peptides and ProteinsLGI1 protein, humanNerve Tissue ProteinsProteinsADAM22assemblycryo-EMepilepsyHS-AFMhumanLGI1molecular biophysicsstructural biology

Identifiers

PMID40601686
PMCPMC12226019

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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.