Evidence map›Paper›PMID 26416531›Full record

ArticleJournal of structural biology2015

Structure of Liver Receptor Homolog-1 (NR5A2) with PIP3 hormone bound in the ligand binding pocket.

Elena P Sablin, Raymond D Blind, Rubatharshini Uthayaruban, Hsiu-Ju Chiu, Ashley M Deacon, Debanu Das, Holly A Ingraham, Robert J Fletterick

Open access · greenAbstract read
In one paragraph

Article in Journal of structural biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
2.4field-weighted citation impact, top 10% 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

38 citing papers in PubMed, 59 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. Review
  7. Review
  8. Review
  9. Article
  10. SF-1 Induces Nuclear PIP2.Biomolecules · 2023
    Article
  11. Article
  12. Article
  13. Review
  14. Genetic Analysis ofGenes · 2022
    Review
  15. Article
  16. Nuclear Receptors and Lipid Sensing.Advances in experimental medicine and biology · 2022
    Article
  17. Article
  18. Review
  19. Article
  20. 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

8 authors at 3 institutions in 1 country.

Elena P SablinDepartment of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, United States.
Raymond D BlindDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, United States.
Rubatharshini UthayarubanDepartment of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, United States.
Hsiu-Ju ChiuJoint Center for Structural Genomics, SLAC National Accelerator Laboratory, Menlo Park, CA 94025, United States; Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, CA 94025, United States.
Ashley M DeaconJoint Center for Structural Genomics, SLAC National Accelerator Laboratory, Menlo Park, CA 94025, United States; Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, CA 94025, United States.
Debanu DasJoint Center for Structural Genomics, SLAC National Accelerator Laboratory, Menlo Park, CA 94025, United States; Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, CA 94025, United States.
Holly A IngrahamDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, United States.
Robert J FletterickDepartment of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, United States. Electronic address: Robert.Fletterick@ucsf.edu.
University of California, San Francisco · USSLAC National Accelerator Laboratory · USStanford Synchrotron Radiation Lightsource · US

Funding

Structure Determination Core at SSRLU54GM094586 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI WILSON, IAN A · 2010 to 2014
$40.1M
X-ray Absorption Spectroscopy (XAS) pp.711-759P41GM103393 · NIGMS · STANFORD UNIVERSITY · PI HODGSON, KEITH O · 2012 to 2019
$30.6M
Research BaseP30DK063720 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GERMAN, MICHAEL S · 2003 to 2019
$21.8M
UCSF IRACDA Scholars ProgramK12GM081266 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Raymond M. Esquerra, HOLLY A. INGRAHAM · 2007 to 2026
$19.4M
UCSF Nutrition Obesity Research CenterP30DK098722 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHRISTIAN VAISSE · 2015 to 2026
$14.6M
Structures of Protein Complexes Regulating Transcription in Enbryonic Stem CellsU01GM094614 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WEBB, PAUL · 2010 to 2014
$5.7M
Mapping Hypothalamic Neurocircuits Controlling Physical ActivityR01DK099722 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI INGRAHAM, HOLLY A. · 2014 to 2018
$2.0M
Structural Analyses of NR5 Orphan Nuclear ReceptorsR01DK072246 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI INGRAHAM, HOLLY A. · 2005 to 2009
$1.7M
Mechanisms of regulation of LRH-1, Nanog and SF-1 by DAX-1R01DK078075 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FLETTERICK, ROBERT J · 2008 to 2011
$1.5M
Cancer cell signaling through lipids complexed to proteinsK01CA172957 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BLIND, RAYMOND DANIEL · 2012 to 2015
$449k
NCI NIH HHS 1K01CA172957NCI NIH HHS K01 CA172957NIDDK NIH HHS P30 DK063720NIDDK NIH HHS P30 DK098722NIDDK NIH HHS R01 DK072246NIDDK NIH HHS R01DK072246NIDDK NIH HHS R01 DK078075NIDDK NIH HHS R01DK078075NIDDK NIH HHS R01 DK099722NIDDK NIH HHS R01DK099722NIGMS NIH HHS K12 GM081266NIGMS NIH HHS K12GM081266NIGMS NIH HHS P41 GM103393NIGMS NIH HHS U01 GM094614NIGMS NIH HHS U54 GM094586
6 · The paper itself

Abstract

The nuclear receptor LRH-1 (Liver Receptor Homolog-1, NR5A2) is a transcription factor that regulates gene expression programs critical for many aspects of metabolism and reproduction. Although LRH-1 is able to bind phospholipids, it is still considered an orphan nuclear receptor (NR) with an unknown regulatory hormone. Our prior cellular and structural studies demonstrated that the signaling phosphatidylinositols PI(4,5)P2 (PIP2) and PI(3,4,5)P3 (PIP3) bind and regulate SF-1 (Steroidogenic Factor-1, NR5A1), a close homolog of LRH-1. Here, we describe the crystal structure of human LRH-1 ligand binding domain (LBD) bound by PIP3 - the first phospholipid with a head group endogenous to mammals. We show that the phospholipid hormone binds LRH-1 with high affinity, stabilizing the receptor LBD. While the hydrophobic PIP3 tails (C16/C16) are buried inside the LRH-1 ligand binding pocket, the negatively charged PIP3 head group is presented on the receptor surface, similar to the phosphatidylinositol binding mode observed in the PIP3-SF-1 structure. Thus, data presented in this work reinforce our earlier findings demonstrating that signaling phosphatidylinositols regulate the NR5A receptors LRH-1 and SF-1.

Indexed as

Binding SitesCrystallography, X-RayDAX-1 Orphan Nuclear ReceptorHumansModels, MolecularPhosphatidylinositolsProtein BindingProtein Structure, TertiaryReceptors, Cytoplasmic and NuclearSteroidogenic Factor 1DAX-1 Orphan Nuclear ReceptorNR0B1 protein, humanNR5A1 protein, humanNR5A2 protein, humanPhosphatidylinositolsReceptors, Cytoplasmic and NuclearSteroidogenic Factor 1Crystal structureLigandLiver Receptor Homolog-1LRH-1NR5A2Nuclear receptorPIP(3)

Identifiers

PMID26416531
PMCPMC4651778
OpenAlexW1804706871

What OpenQuestion holds

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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.