Evidence map›Paper›PMID 40124498›Full record

ReviewiScience2025

Evolving concepts of the protein universe.

Prakash Kulkarni, Lauren Porter, Tsui-Fen Chou, Shasha Chong, Fabrizio Chiti, Joseph W Schafer, Atish Mohanty, Sravani Ramisetty, Jose N Onuchic, Mick Tuite and 5 more

Abstract readReview
In one paragraph

Review in iScience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Shining light on the dark proteome with unstructural biology.Current research in structural biology · 2026
    Article
  5. Review
  6. Article
  7. Review
  8. Review
  9. Review
  10. Review
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

15 authors.

Prakash KulkarniDepartment of Medical Oncology, City of Hope Medical Center, Duarte, CA, USA.
Lauren PorterNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.
Tsui-Fen ChouDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Shasha ChongDivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA.
Fabrizio ChitiDepartment of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy.
Joseph W SchaferNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.
Atish MohantyDepartment of Medical Oncology, City of Hope Medical Center, Duarte, CA, USA.
Sravani RamisettyDepartment of Medical Oncology, City of Hope Medical Center, Duarte, CA, USA.
Jose N OnuchicCenter for Theoretical Biological Physics, Rice University, Houston, TX, USA.
Mick TuiteKent Fungal Group, School of Biosciences, Division of Natural Sciences, University of Kent, CT2 7NJ Canterbury, UK.
Vladimir N UverskyDepartment of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Keith R WeningerDepartment of Physics, North Carolina State University, Raleigh, NC, USA.
Eugene V KooninNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.
John OrbanW. M. Keck Laboratory for Structural Biology, University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, MD, USA.
Ravi SalgiaDepartment of Medical Oncology, City of Hope Medical Center, Duarte, CA, USA.

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Robert Damoiseaux · 1985 to 2026
$134.5M
Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI John Charles Williams · 1985 to 2026
$86.3M
Structure and stability of 3_alpha vs alpha_beta foldsR01GM062154 · NIGMS · UNIV OF MARYLAND, COLLEGE PARK · PI BRYAN, PHILIP N, ORBAN, JOHN · 2002 to 2016
$3.2M
Engineering protein-specific proteases: targeting signaling proteinsR01GM141290 · NIGMS · UNIV OF MARYLAND, COLLEGE PARK · PI BRYAN, PHILIP N, ORBAN, JOHN · 2021 to 2024
$2.3M
Molecular Mechanisms of DNA Mismatch Repair InitiationR01GM132263 · NIGMS · NORTH CAROLINA STATE UNIVERSITY RALEIGH · PI WENINGER, KEITH R · 2019 to 2022
$1.2M
NCI NIH HHS P30 CA016042NCI NIH HHS P30 CA033572NIGMS NIH HHS R01 GM062154NIGMS NIH HHS R01 GM132263NIGMS NIH HHS R01 GM141290
6 · The paper itself

Abstract

The protein universe is the collection of all proteins on earth from all organisms both extant and extinct. Classical studies on protein folding suggested that proteins exist as a unique three-dimensional conformation that is dictated by the genetic code and is critical for function. In this perspective, we discuss ideas and developments that emerged over the past three decades regarding the protein structure-function paradigm. It is now clear that ordered (active/functional) and disordered/denatured (and hence inactive/non-functional) represent a continuum of states rather than binary states. Some proteins can switch folds without sequence change. Others exist as conformational ensembles lacking defined structure yet play critical roles in many biological processes, including forming membrane-less organelles driven by liquid-liquid phase separation. Numerous diverse proteins harbor segments with the potential to form amyloid fibrils, many of which are functional, and some possess prion-like properties enabling conformation-based transfer of heritable information. Taken together, these developments reveal the remarkable complexity of the protein universe.

Indexed as

BiochemistryBiological sciencesProteinStructural biology

Identifiers

PMID40124498
PMCPMC11926713

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.