Evidence map›Paper›PMID 19251697›Full record

ArticleThe Journal of biological chemistry2009

Real-time analysis of conformation-sensitive antibody binding provides new insights into integrin conformational regulation.

Alexandre Chigaev, Anna Waller, Or Amit, Liliana Halip, Cristian G Bologa, Larry A Sklar

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
3.8field-weighted citation impact, top 6% 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

37 citing papers in PubMed, 56 citations in OpenAlex.

  1. Article
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  4. A humanized βCell reports · 2022
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  5. Experimental and therapeutic medicine · 2022
    Article
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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

6 authors at 2 institutions in 2 countries.

Alexandre ChigaevDepartment of Pathology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131, USA. achigaev@salud.unm.edu
Anna Waller
Or Amit
Liliana Halip
Cristian G Bologa
Larry A Sklar
New Mexico Cancer Center · USUniversity of New Mexico · US

Funding

Regulation of mucous cell metaplasia in asthmaP50HL056384 · NHLBI · UNIVERSITY OF NEW MEXICO · PI LIPSCOMB, MARY FISHER · 1997 to 2006
$9.7M
Force, Conformation & Affinity in VLA-4 and LFA-1 AdhesionR01HL081062 · NHLBI · UNIVERSITY OF NEW MEXICO · PI SKLAR, LARRY A. · 2007 to 2011
$2.4M
NHLBI NIH HHS HL081062NHLBI NIH HHS HL56384NHLBI NIH HHS R01 HL081062
6 · The paper itself

Abstract

Integrins are heterodimeric adhesion receptors that regulate immune cell adhesion. Integrin-dependent adhesion is controlled by multiple conformational states that include states with different affinity to the ligand, states with various degrees of molecule unbending, and others. Affinity change and molecule unbending play major roles in the regulation of cell adhesion. The relationship between different conformational states of the integrin is unclear. Here we have used conformationally sensitive antibodies and a small LDV-containing ligand to study the role of the inside-out signaling through formyl peptide receptor and CXCR4 in the regulation of alpha(4)beta(1) integrin conformation. We found that in the absence of ligand, activation by formyl peptide or SDF-1 did not result in a significant exposure of HUTS-21 epitope. Occupancy of the ligand binding pocket without cell activation was sufficient to induce epitope exposure. EC(50) for HUTS-21 binding in the presence of LDV was identical to a previously reported ligand equilibrium dissociation constant at rest and after activation. Furthermore, the rate of HUTS-21 binding was also related to the VLA-4 activation state even at saturating ligand concentration. We propose that the unbending of the integrin molecule after guanine nucleotide-binding protein-coupled receptor-induced signaling accounts for the enhanced rate of HUTS-21 binding. Taken together, current results support the existence of multiple conformational states independently regulated by both inside-out signaling and ligand binding. Our data suggest that VLA-4 integrin hybrid domain movement does not depend on the affinity state of the ligand binding pocket.

Indexed as

AntibodiesBinding SitesCell Line, TumorEpitopesHumansIntegrin alpha4Integrin alpha4beta1IntegrinsKineticsLigandsModels, MolecularMutant ProteinsProtein ConformationReceptors, CXCR4Receptors, Formyl PeptideTime FactorsAntibodiesEpitopesIntegrin alpha4Integrin alpha4beta1IntegrinsLigandsMutant ProteinsReceptors, CXCR4Receptors, Formyl Peptide

Identifiers

PMID19251697
PMCPMC2682882
OpenAlexW2081033022

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.