Evidence map›Paper›PMID 26087144›Full record

ArticleJournal of molecular biology2015

Engineering Synthetic Antibody Inhibitors Specific for LD2 or LD4 Motifs of Paxillin.

Malgorzata Nocula-Lugowska, Mateusz Lugowski, Ravi Salgia, Anthony A Kossiakoff

Open access · greenAbstract read
In one paragraph

Article in Journal of molecular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.3field-weighted citation impact, top 38% 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

7 citing papers in PubMed, 10 citations in OpenAlex.

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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

4 authors at 1 institution in 1 country.

Malgorzata Nocula-LugowskaDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60607, USA.
Mateusz LugowskiDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60607, USA.
Ravi SalgiaDepartment of Medicine, The University of Chicago, Chicago, IL 60637, USA.
Anthony A KossiakoffDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60607, USA. Electronic address: koss@bsd.uchicago.edu.
University of Chicago · US

Funding

Foreign - Univ. of Toronto, PI-Dr. Sachdev SidhuU01GM094588 · NIGMS · UNIVERSITY OF CHICAGO · PI KOSSIAKOFF, ANTHONY A · 2010 to 2014
$6.8M
NIGMS NIH HHS U01 GM094588
6 · The paper itself

Abstract

Focal adhesion protein paxillin links integrin and growth factor signaling to actin cytoskeleton. Most of paxillin signaling activity is regulated via leucine-rich LD motifs (LD1-LD5) located at the N-terminus. Here, we demonstrate a method to engineer highly selective synthetic antibodies (sABs) against LD2 and LD4 that are binding sites for focal adhesion kinase (FAK) and other proteins. Phage display selections against peptides were used to generate sABs recognizing each LD motif. In the obtained X-ray crystal structures of the LD-sAB complexes, the LD motifs are helical and bind sABs through a hydrophobic side, similarly as in the structures with natural paxillin partners. The sABs are capable of pulling down endogenous paxillin in complex with FAK and can visualize paxillin in focal adhesions in cells. They were also used as selective inhibitors to effectively compete with focal adhesion targeting domain of FAK for the binding to LD2 and LD4. The sABs are tools for investigation of paxillin LD binding "platforms" and are capable of inhibiting paxillin interactions, thereby useful as potential therapeutics in the future.

Indexed as

Protein EngineeringAmino Acid MotifsAmino Acid SequenceAntibodies, MonoclonalBinding SitesCell Surface Display TechniquesCrystallography, X-RayFocal Adhesion Protein-Tyrosine KinasesHumansModels, MolecularPaxillinProtein BindingProtein Interaction Domains and MotifsProtein Structure, QuaternaryAntibodies, MonoclonalFocal Adhesion Protein-Tyrosine KinasesPaxillinfocal adhesionpaxillinphage displayprotein–protein interactionsynthetic antigen binder

Identifiers

PMID26087144
PMCPMC4521624
OpenAlexW1838780003

What OpenQuestion holds

Textmetadata
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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.