Evidence map›Paper›PMID 27317747›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Relating conformation to function in integrin α5β1.

Yang Su, Wei Xia, Jing Li, Thomas Walz, Martin J Humphries, Dietmar Vestweber, Carlos Cabañas, Chafen Lu, Timothy A Springer

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed
11.1field-weighted citation impact, top 1% 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

94 citing papers in PubMed, 139 citations in OpenAlex.

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  11. Spatial N-glycan rearrangement on αNature communications · 2025
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34 more citing papers are in PubMed but not listed here.

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

9 authors at 6 institutions in 4 countries.

Yang SuProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115;
Wei XiaProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115;
Jing LiProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115;
Thomas WalzRockefeller University, New York, NY 10065;
Martin J HumphriesWellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom;
Dietmar VestweberMax Planck Institute of Molecular Biomedicine, 48149 Muenster, Germany;
Carlos CabañasCentro de Biología Molecular Severo Ochoa (CSIC-UAM), 28049 Madrid, Spain.
Chafen LuProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115;
Timothy A SpringerProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115; timothy.springer@childrens.harvard.edu.
Boston Children's Hospital · USHarvard University · USCentro de Biología Molecular Severo Ochoa · ESMax Planck Institute for Molecular Biomedicine · DERockefeller University · USWellcome Centre for Cell-Matrix Research · GB

Funding

Structures and Conformational Equilibria of Integrin alpha5 beta1R01HL131729 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI SPRINGER, TIMOTHY A · 2016 to 2024
$4.7M
Single molecule measurements on von Willebrand factor A1 and A2 domainsR01HL108248 · NHLBI · IMMUNE DISEASE INSTITUTE, INC. · PI SPRINGER, TIMOTHY A · 2011 to 2015
$2.4M
NHLBI NIH HHS R01 HL108248NHLBI NIH HHS R01 HL131729
6 · The paper itself

Abstract

Whether β1 integrin ectodomains visit conformational states similarly to β2 and β3 integrins has not been characterized. Furthermore, despite a wealth of activating and inhibitory antibodies to β1 integrins, the conformational states that these antibodies stabilize, and the relation of these conformations to function, remain incompletely characterized. Using negative-stain electron microscopy, we show that the integrin α5β1 ectodomain adopts extended-closed and extended-open conformations as well as a bent conformation. Antibodies SNAKA51, 8E3, N29, and 9EG7 bind to different domains in the α5 or β1 legs, activate, and stabilize extended ectodomain conformations. Antibodies 12G10 and HUTS-4 bind to the β1 βI domain and hybrid domains, respectively, activate, and stabilize the open headpiece conformation. Antibody TS2/16 binds a similar epitope as 12G10, activates, and appears to stabilize an open βI domain conformation without requiring extension or hybrid domain swing-out. mAb13 and SG/19 bind to the βI domain and βI-hybrid domain interface, respectively, inhibit, and stabilize the closed conformation of the headpiece. The effects of the antibodies on cell adhesion to fibronectin substrates suggest that the extended-open conformation of α5β1 is adhesive and that the extended-closed and bent-closed conformations are nonadhesive. The functional effects and binding sites of antibodies and fibronectin were consistent with their ability in binding to α5β1 on cell surfaces to cross-enhance or inhibit one another by competitive or noncompetitive (allosteric) mechanisms.

Indexed as

Escherichia coliFibronectinsHumansIntegrin alpha5beta1Protein ConformationStructure-Activity RelationshipFibronectinsIntegrin alpha5beta1

Identifiers

PMID27317747
PMCPMC4941492
OpenAlexW2433805774

What OpenQuestion holds

Textmetadata
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.