Evidence map›Paper›PMID 35443068›Full record

ArticleProteins2022

IGF-dependent dynamic modulation of a protease cleavage site in the intrinsically disordered linker domain of human IGFBP2.

Garima Jaipuria, Divya Shet, Shahid Malik, Monalisa Swain, Hanudatta S Atreya, Charles A Galea, Mark G Slomiany, Steven A Rosenzweig, Briony E Forbes, Raymond S Norton and 1 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proteins, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.7field-weighted citation impact, top 29% 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

5 citing papers in PubMed, 5 citations in OpenAlex.

  1. Solution-state nuclear magnetic resonance studies of theBiochemistry and biophysics reports · 2026
    Article
  2. Article
  3. Article
  4. Carbon quantum dots in bioimaging and biomedicines.Frontiers in bioengineering and biotechnology · 2023
    Review
  5. Structure of the PAPP-ANature communications · 2022
    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

11 authors at 8 institutions in 4 countries.

Garima JaipuriaNMR Research Centre, Indian Institute of Science, Bangalore, Karnataka, India.
Divya ShetNMR Research Centre, Indian Institute of Science, Bangalore, Karnataka, India.
Shahid MalikNMR Research Centre, Indian Institute of Science, Bangalore, Karnataka, India.
Monalisa SwainNMR Research Centre, Indian Institute of Science, Bangalore, Karnataka, India.
Hanudatta S Atreya
Charles A GaleaMedicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Parkville, Australia.
Mark G SlomianyDepartment of Cell and Molecular Pharmacology, Medical University of South Carolina, Charleston, South Carolina, USA.
Steven A RosenzweigDepartment of Cell and Molecular Pharmacology, Medical University of South Carolina, Charleston, South Carolina, USA.
Briony E ForbesFlinders Health and Medical Research Institute, Flinders University, South Australia, Australia.
Raymond S NortonMedicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Parkville, Australia.
Somnath MondalNMR Research Centre, Indian Institute of Science, Bangalore, Karnataka, India.ORCID 0000-0002-5657-8077
Indian Institute of Science Bangalore · INMedical University of South Carolina · USFlinders University · AUFrederick National Laboratory for Cancer Research · USMonash Institute of Medical Research · AUMonash University · AURaman Research Institute · INUniversité de Bordeaux · FR

Funding

Translational Science Laboratory Shared ResourceP30CA138313 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI John J Lemasters · 2009 to 2026
$42.7M
NCI NIH HHS P30 CA138313
6 · The paper itself

Abstract

Functional regulation via conformational dynamics is well known in structured proteins but less well characterized in intrinsically disordered proteins and their complexes. Using NMR spectroscopy, we have identified a dynamic regulatory mechanism in the human insulin-like growth factor (IGF) system involving the central, intrinsically disordered linker domain of human IGF-binding protein-2 (hIGFBP2). The bioavailability of IGFs is regulated by the proteolysis of IGF-binding proteins. In the case of hIGFBP2, the linker domain (L-hIGFBP2) retains its intrinsic disorder upon binding IGF-1, but its dynamics are significantly altered, both in the IGF binding region and distantly located protease cleavage sites. The increase in flexibility of the linker domain upon IGF-1 binding may explain the IGF-dependent modulation of proteolysis of IGFBP2 in this domain. As IGF homeostasis is important for cell growth and function, and its dysregulation is a key contributor to several cancers, our findings open up new avenues for the design of IGFBP analogs inhibiting IGF-dependent tumors.

Indexed as

Insulin-Like Growth Factor Binding Protein 2Insulin-Like Growth Factor IIntrinsically Disordered ProteinsHumansPeptide HydrolasesProtein BindingIGFBP2 protein, humanInsulin-Like Growth Factor Binding Protein 2Insulin-Like Growth Factor IIntrinsically Disordered ProteinsPeptide Hydrolasesconformational dynamics of intrinsically disordered proteindisordered proteinfunction-dynamics relationship of disordered proteinhuman IGF-binding protein-2human insulin-like growth factor systemintrinsically disordered proteinNMRprotein-NMRprotein-protein interactionproteolysis

Identifiers

PMID35443068
PMCPMC9357107
OpenAlexW4225259019

What OpenQuestion holds

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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.