Evidence map›Paper›PMID 31353240›Full record

ArticleStructure (London, England : 1993)2019

Structural Basis of the Differential Binding of Engineered Knottins to Integrins αVβ3 and α5β1.

Johannes F Van Agthoven, Hengameh Shams, Frank V Cochran, José L Alonso, James R Kintzing, Kiavash Garakani, Brian D Adair, Jian-Ping Xiong, Mohammad R K Mofrad, Jennifer R Cochran and 1 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Structure (London, England : 1993), 2019. 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
1.1field-weighted citation impact, top 25% 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

10 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. 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

11 authors at 3 institutions in 1 country.

Johannes F Van AgthovenLeukocyte Biology and Inflammation Program, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA; Structural Biology Program, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA; Division of Nephrology/Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Hengameh ShamsDepartments of Bioengineering and Mechanical Engineering, University of California, Berkeley, CA 94720, USA.
Frank V CochranDepartments of Bioengineering and Chemical Engineering, Stanford University, Stanford, CA 94305, USA.
José L AlonsoLeukocyte Biology and Inflammation Program, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA; Structural Biology Program, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA; Division of Nephrology/Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
James R KintzingDepartments of Bioengineering and Chemical Engineering, Stanford University, Stanford, CA 94305, USA.
Kiavash GarakaniDepartments of Bioengineering and Mechanical Engineering, University of California, Berkeley, CA 94720, USA.
Brian D AdairLeukocyte Biology and Inflammation Program, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA; Structural Biology Program, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA; Division of Nephrology/Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Jian-Ping XiongLeukocyte Biology and Inflammation Program, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA; Structural Biology Program, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA; Division of Nephrology/Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Mohammad R K MofradDepartments of Bioengineering and Mechanical Engineering, University of California, Berkeley, CA 94720, USA.
Jennifer R CochranDepartments of Bioengineering and Chemical Engineering, Stanford University, Stanford, CA 94305, USA.
M Amin ArnaoutLeukocyte Biology and Inflammation Program, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA; Structural Biology Program, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA; Division of Nephrology/Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA. Electronic address: aarnaout1@mgh.harvard.edu.
Harvard University · USStanford University · USUniversity of California, Berkeley · US

Funding

Structure and Function of beta2 IntegrinR01DK048549 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI ARNAOUT, M. AMIN · 1994 to 2016
$6.0M
Structure and Function of Integrins in the KidneyR01DK088327 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI ARNAOUT, M. AMIN · 2010 to 2025
$5.3M
Novel Features of Integrin Antagonism Applied to Renal DysfunctionK01DK101628 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI VAN AGTHOVEN, JOHANNES FRANCISCUS · 2015 to 2019
$797k
NIDDK NIH HHS K01 DK101628NIDDK NIH HHS R01 DK048549NIDDK NIH HHS R01 DK088327
6 · The paper itself

Abstract

Targeting both integrins αVβ3 and α5β1 simultaneously appears to be more effective in cancer therapy than targeting each one alone. The structural requirements for bispecific binding of ligand to integrins have not been fully elucidated. RGD-containing knottin 2.5F binds selectively to αVβ3 and α5β1, whereas knottin 2.5D is αVβ3 specific. To elucidate the structural basis of this selectivity, we determined the structures of 2.5F and 2.5D as apo proteins and in complex with αVβ3, and compared their interactions with integrins using molecular dynamics simulations. These studies show that 2.5D engages αVβ3 by an induced fit, but conformational selection of a flexible RGD loop accounts for high-affinity selective binding of 2.5F to both integrins. The contrasting binding of the highly flexible low-affinity linear RGD peptides to multiple integrins suggests that a "Goldilocks zone" of conformational flexibility of the RGD loop in 2.5F underlies its selective binding promiscuity to integrins.

Indexed as

Binding SitesCystine-Knot MiniproteinsHumansIntegrin alphaVbeta3K562 CellsModels, MolecularMolecular Dynamics SimulationMutationProtein BindingProtein ConformationReceptors, VitronectinCystine-Knot Miniproteinsintegrin alphavbeta1Integrin alphaVbeta3Receptors, Vitronectincancer diagnosiscancer therapycell adhesionconformational flexibilityintegrinsmolecular dynamicsNMRprotein crystallographyreceptors/structure-function

Identifiers

PMID31353240
PMCPMC6726563
OpenAlexW2962750724

What OpenQuestion holds

Textmetadata
LicenceTDM
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.