Evidence map›Paper›PMID 40106358›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

Structural assembly of the PAS domain drives the catalytic activation of metazoan PASK.

Sajina Dhungel, Michael Xiao, Rajesh Rajaian Pushpabai, Chintan K Kikani

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

4 authors.

Sajina DhungelDepartment of Biology, University of Kentucky, Lexington, KY 40502.
Michael XiaoDepartment of Biology, University of Kentucky, Lexington, KY 40502.
Rajesh Rajaian PushpabaiDepartment of Biology, University of Kentucky, Lexington, KY 40502.
Chintan K KikaniDepartment of Biology, University of Kentucky, Lexington, KY 40502.ORCID 0000-0003-1140-0192

Funding

Epigenetic control of muscle stem cell function by PASK-Wdr5 signalingR01AR073906 · NIAMS · UNIVERSITY OF KENTUCKY · PI KIKANI, CHINTAN K · 2019 to 2024
$1.6M
HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) R01AR073906NIAMS NIH HHS R01 AR073906
6 · The paper itself

Abstract

PAS domains are ubiquitous sensory modules that transduce environmental signals into cellular responses through tandem PAS folds and PAS-associated C-terminal (PAC) motifs. While this conserved architecture underpins their regulatory roles, here we uncover a structural divergence in the metazoan PAS domain-regulated kinase (PASK). By integrating evolutionary-scale domain mapping with deep learning-based structural models, we identified two PAS domains in PASK, namely PAS-B and PAS-C, in addition to the previously known PAS-A domain. Unlike canonical PAS domains, the PAS fold and PAC motif in the PAS-C domain are spatially segregated by an unstructured linker, yet a functional PAS module is assembled through intramolecular interactions. We demonstrate that this assembly is nutrient responsive and serves to remodel the quaternary structure of PASK that positions the PAS-A domain near the kinase activation loop. This nutrient-sensitive spatial arrangement stabilizes the activation loop, enabling catalytic activation of PASK. These findings revealed an alternative mode of regulatory control in PAS sensory proteins, where the structural assembly of PAS domains links environmental sensing to enzymatic activity. By demonstrating that PAS domains integrate signals through dynamic structural rearrangements, this study broadens the understanding of their functional and regulatory roles and highlights potential opportunities for targeting PAS domain-mediated pathways in therapeutic applications.

Indexed as

Protein Serine-Threonine KinasesAnimalsCatalytic DomainEnzyme ActivationHumansModels, MolecularProtein DomainsPAS domain kinasesProtein Serine-Threonine KinasesAlphaFoldmTORmyogenesisPAS domainPASK

Identifiers

PMID40106358
PMCPMC11962487

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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.