Evidence map›Paper›PMID 36346217›Full record

ArticleeLife2022

Integrative modeling reveals the molecular architecture of the intraflagellar transport A (IFT-A) complex.

Caitlyn L McCafferty, Ophelia Papoulas, Mareike A Jordan, Gabriel Hoogerbrugge, Candice Nichols, Gaia Pigino, David W Taylor, John B Wallingford, Edward M Marcotte

Open access · goldAbstract read
In one paragraph

Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
6.4field-weighted citation impact, top 3% 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

27 citing papers in PubMed, 35 citations in OpenAlex.

  1. Preclinical human models of primary ciliary dyskinesia.European respiratory review : an official journal of the European Respiratory Society · 2026
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  12. AlphaFold two years on: Validation and impact.Proceedings of the National Academy of Sciences of the United States of America · 2024
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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 at 2 institutions in 2 countries.

Caitlyn L McCaffertyDepartment of Molecular Biosciences, Center for Systems and Synthetic Biology, University of Texas, Austin, United States.ORCID 0000-0002-0872-4527
Ophelia PapoulasDepartment of Molecular Biosciences, Center for Systems and Synthetic Biology, University of Texas, Austin, United States.ORCID 0000-0002-6370-0616
Mareike A JordanMax Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.ORCID 0000-0001-6248-8863
Gabriel HoogerbruggeDepartment of Molecular Biosciences, Center for Systems and Synthetic Biology, University of Texas, Austin, United States.ORCID 0000-0001-7617-3168
Candice NicholsDepartment of Molecular Biosciences, Center for Systems and Synthetic Biology, University of Texas, Austin, United States.
Gaia PiginoHuman Technopole, Milan, Italy.ORCID 0000-0002-2295-9568
David W TaylorDepartment of Molecular Biosciences, Center for Systems and Synthetic Biology, University of Texas, Austin, United States.ORCID 0000-0002-6198-1194
John B WallingfordDepartment of Molecular Biosciences, Center for Systems and Synthetic Biology, University of Texas, Austin, United States.ORCID 0000-0002-6280-8625
Edward M MarcotteDepartment of Molecular Biosciences, Center for Systems and Synthetic Biology, University of Texas, Austin, United States.ORCID 0000-0001-8808-180X
Human Technopole · ITMax Planck Institute of Molecular Cell Biology and Genetics · DE

Funding

Mapping the CPLANE interactome, an extensive protein interaction network underlying human ciliopathiesR01HD085901 · NICHD · UNIVERSITY OF TEXAS AT AUSTIN · PI EDWARD M MARCOTTE, John B Wallingford · 2016 to 2026
$6.2M
Proteomics and model organism humanization to decode human geneticsR35GM122480 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI EDWARD M MARCOTTE · 2017 to 2026
$5.4M
Imaging macromolecular machines in gene regulationR35GM138348 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI TAYLOR, DAVID W · 2020 to 2024
$1.9M
6 · The paper itself

Abstract

Intraflagellar transport (IFT) is a conserved process of cargo transport in cilia that is essential for development and homeostasis in organisms ranging from algae to vertebrates. In humans, variants in genes encoding subunits of the cargo-adapting IFT-A and IFT-B protein complexes are a common cause of genetic diseases known as ciliopathies. While recent progress has been made in determining the atomic structure of IFT-B, little is known of the structural biology of IFT-A. Here, we combined chemical cross-linking mass spectrometry and cryo-electron tomography with AlphaFold2-based prediction of both protein structures and interaction interfaces to model the overall architecture of the monomeric six-subunit IFT-A complex, as well as its polymeric assembly within cilia. We define monomer-monomer contacts and membrane-associated regions available for association with transported cargo, and we also use this model to provide insights into the pleiotropic nature of human ciliopathy-associated genetic variants in genes encoding IFT-A subunits. Our work demonstrates the power of integration of experimental and computational strategies both for multi-protein structure determination and for understanding the etiology of human genetic disease.

Indexed as

CiliaCiliopathiesAnimalsBiological TransportElectron Microscope TomographyHomeostasisHumansbiochemistrychemical biologychlamydomonas reinhardtiicross-linking mass spectrometryhomo sapiensintegrative structural biologyintraflagellar transportmolecular biophysicsmotile ciliastructural biologytetrahymena thermophila

Identifiers

PMID36346217
PMCPMC9674347
OpenAlexW4308555726

What OpenQuestion holds

Textmetadata
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.