Evidence map›Paper›PMID 38746453›Full record

ArticlebioRxiv : the preprint server for biology2024

Molecular basis for plasma membrane recruitment of PI4KA by EFR3.

Sushant Suresh, Alexandria L Shaw, Joshua G Pemberton, Mackenzie K Scott, Noah J Harris, Matthew Ah Parson, Meredith L Jenkins, Pooja Rohilla, Alejandro Alvarez-Prats, Tamas Balla and 2 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Sushant SureshDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, BC, V8W 2Y2, Canada.
Alexandria L ShawDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, BC, V8W 2Y2, Canada.
Joshua G PembertonSection on Molecular Signal Transduction, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States.
Mackenzie K ScottDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, BC, V8W 2Y2, Canada.
Noah J HarrisDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, BC, V8W 2Y2, Canada.
Matthew Ah ParsonDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, BC, V8W 2Y2, Canada.
Meredith L JenkinsDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, BC, V8W 2Y2, Canada.
Pooja RohillaSection on Molecular Signal Transduction, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States.
Alejandro Alvarez-PratsSection on Molecular Signal Transduction, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States.
Tamas BallaSection on Molecular Signal Transduction, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States.
Calvin K YipDepartment of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
John E BurkeDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, BC, V8W 2Y2, Canada.ORCID 0000-0001-7904-9859

Funding

PHOSPHOINOSITIDE-CALCIUM SIGNALING IN CELL REGULATIONZ01HD000196 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI BALLA, TAMAS · 1998 to 2008
$1.9M
Intramural NIH HHS Z01 HD000196
6 · The paper itself

Abstract

The lipid kinase phosphatidylinositol 4 kinase III alpha (PI4KIIIa/PI4KA) is a master regulator of the lipid composition and asymmetry of the plasma membrane. PI4KA exists primarily in a heterotrimeric complex with its regulatory proteins TTC7 and FAM126. Fundamental to PI4KA activity is its targeted recruitment to the plasma membrane by the lipidated proteins EFR3A and EFR3B. Here, we report a cryo-EM structure of the C-terminus of EFR3A bound to the PI4KA-TTC7B-FAM126A complex, with extensive validation using both hydrogen deuterium exchange mass spectrometry (HDX-MS), and mutational analysis. The EFR3A C-terminus undergoes a disorder-order transition upon binding to the PI4KA complex, with an unexpected direct interaction with both TTC7B and FAM126A. Complex disrupting mutations in TTC7B, FAM126A, and EFR3 decrease PI4KA recruitment to the plasma membrane. Multiple post-translational modifications and disease linked mutations map to this site, providing insight into how PI4KA membrane recruitment can be regulated and disrupted in human disease.

Identifiers

PMID38746453
PMCPMC11092606

What OpenQuestion holds

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Registered trials

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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.