Evidence map›Paper›PMID 28771403›Full record

ArticleeLife2017

Structural insight into the activation of a class B G-protein-coupled receptor by peptide hormones in live human cells.

Lisa Seidel, Barbara Zarzycka, Saheem A Zaidi, Vsevolod Katritch, Irene Coin

Open access · goldAbstract read
In one paragraph

Article in eLife, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

25 citing papers in PubMed, 55 citations in OpenAlex.

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  15. Genetically encoded crosslinkers to address protein-protein interactions.Protein science : a publication of the Protein Society · 2023
    Review
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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

5 authors at 2 institutions in 2 countries.

Lisa SeidelInstitute of Biochemistry, Leipzig University, Leipzig, Germany.ORCID 0000-0003-0020-1315
Barbara ZarzyckaDepartment of Biological Sciences, Bridge Institute, University of Southern California, Los Angeles, United States.ORCID 0000-0002-7202-5317
Saheem A ZaidiDepartment of Biological Sciences, Bridge Institute, University of Southern California, Los Angeles, United States.
Vsevolod KatritchDepartment of Biological Sciences, Bridge Institute, University of Southern California, Los Angeles, United States.ORCID 0000-0003-3883-4505
Irene CoinInstitute of Biochemistry, Leipzig University, Leipzig, Germany.ORCID 0000-0002-7722-004X
University of Southern California · USLeipzig University · DE

Funding

Project 3U54GM094618 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI STEVENS, RAYMOND C · 2010 to 2014
$17.1M
NIGMS NIH HHS U54 GM094618
6 · The paper itself

Abstract

The activation mechanism of class B G-protein-coupled receptors (GPCRs) remains largely unknown. To characterize conformational changes induced by peptide hormones, we investigated interactions of the class B corticotropin-releasing factor receptor type 1 (CRF1R) with two peptide agonists and three peptide antagonists obtained by N-truncation of the agonists. Surface mapping with genetically encoded photo-crosslinkers and pair-wise crosslinking revealed distinct footprints of agonists and antagonists on the transmembrane domain (TMD) of CRF1R and identified numerous ligand-receptor contact sites, directly from the intact receptor in live human cells. The data enabled generating atomistic models of CRF- and CRF(12-41)-bound CRF1R, further explored by molecular dynamics simulations. We show that bound agonist and antagonist adopt different folds and stabilize distinct TMD conformations, which involves bending of helices VI and VII around flexible glycine hinges. Conservation of these glycine hinges among all class B GPCRs suggests their general role in activation of these receptors.

Indexed as

Binding SitesCorticotropin-Releasing HormoneCRF Receptor, Type 1Cross-Linking ReagentsHEK293 CellsHumansLigandsModels, MolecularMolecular Dynamics SimulationProtein BindingProtein DomainsProtein Structure, SecondaryReceptors, Corticotropin-Releasing HormoneCorticotropin-Releasing HormoneCRF Receptor, Type 1Cross-Linking ReagentsLigandsReceptors, Corticotropin-Releasing Hormonebiochemistrybioorthogonal crosslinkingbiophysicsclass B GPCRsexpanded genetic codehumanmolecular modelingorthosteric antagonismpeptide ligandsstructural biology

Identifiers

PMID28771403
PMCPMC5542768
OpenAlexW2743842660

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.