Evidence map›Paper›PMID 35076015›Full record

ArticleeLife2022

Native proline-rich motifs exploit sequence context to target actin-remodeling Ena/VASP protein ENAH.

Theresa Hwang, Sara S Parker, Samantha M Hill, Robert A Grant, Meucci W Ilunga, Venkatesh Sivaraman, Ghassan Mouneimne, Amy E Keating

Open access · goldAbstract read
In one paragraph

Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

17 citing papers in PubMed, 27 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

8 authors at 2 institutions in 1 country.

Theresa HwangDepartment of Biology, Massachusetts Institute of Technology, Cambridge, United States.
Sara S ParkerDepartment of Cellular & Molecular Medicine, University of Arizona, Tucson, United States.ORCID 0000-0003-3670-6147
Samantha M HillDepartment of Cellular & Molecular Medicine, University of Arizona, Tucson, United States.ORCID 0000-0002-6454-7430
Robert A GrantDepartment of Biology, Massachusetts Institute of Technology, Cambridge, United States.ORCID 0000-0002-5072-2867
Meucci W IlungaDepartment of Biology, Massachusetts Institute of Technology, Cambridge, United States.
Venkatesh SivaramanDepartment of Biology, Massachusetts Institute of Technology, Cambridge, United States.
Ghassan MouneimneDepartment of Cellular & Molecular Medicine, University of Arizona, Tucson, United States.ORCID 0000-0001-8103-4701
Amy E KeatingDepartment of Biology, Massachusetts Institute of Technology, Cambridge, United States.ORCID 0000-0003-4074-8980
Massachusetts Institute of Technology · USUniversity of Arizona · US

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Paula T Hammond · 1985 to 2026
$93.9M
PRE-DOCTORAL TRAINING IN THE BIOLOGICAL SCIENCEST32GM007287 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BELL, STEPHEN P., KEATING, AMY E · 1985 to 2019
$40.8M
User Training and OutreachP30GM124165 · NIGMS · CORNELL UNIVERSITY · PI Nozomi Ando, J Christopher Fromme · 2018 to 2026
$34.2M
Pixel Array Detector for Macromolecular CrystallographyS10OD021527 · OD · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2016 to 2016
$2.0M
Novel Mechanism of Breast Cancer Invasion Prevention by Estrogen ReceptorR01CA196885 · NCI · UNIVERSITY OF ARIZONA · PI MOUNEIMNE, GHASSAN · 2015 to 2019
$1.9M
Mapping, modeling and manipulating the interactions of protein domains that bind short linear motifsR01GM129007 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI KEATING, AMY E · 2018 to 2021
$1.4M
NCI NIH HHS P30 CA014051NCI NIH HHS R01 CA196885NIGMS NIH HHS P30 GM124165NIGMS NIH HHS R01 GM129007NIGMS NIH HHS T32 GM007287NIH HHS S10 OD021527
6 · The paper itself

Abstract

The human proteome is replete with short linear motifs (SLiMs) of four to six residues that are critical for protein-protein interactions, yet the importance of the sequence surrounding such motifs is underexplored. We devised a proteomic screen to examine the influence of SLiM sequence context on protein-protein interactions. Focusing on the EVH1 domain of human ENAH, an actin regulator that is highly expressed in invasive cancers, we screened 36-residue proteome-derived peptides and discovered new interaction partners of ENAH and diverse mechanisms by which context influences binding. A pocket on the ENAH EVH1 domain that has diverged from other Ena/VASP paralogs recognizes extended SLiMs and favors motif-flanking proline residues. Many high-affinity ENAH binders that contain two proline-rich SLiMs use a noncanonical site on the EVH1 domain for binding and display a thermodynamic signature consistent with the two-motif chain engaging a single domain. We also found that photoreceptor cilium actin regulator (PCARE) uses an extended 23-residue region to obtain a higher affinity than any known ENAH EVH1-binding motif. Our screen provides a way to uncover the effects of proteomic context on motif-mediated binding, revealing diverse mechanisms of control over EVH1 interactions and establishing that SLiMs can't be fully understood outside of their native context.

Indexed as

Binding SitesActinsCell Adhesion MoleculesDNA-Binding ProteinsHEK293 CellsHumansMicrofilament ProteinsProlineProteomicsActinsCell Adhesion MoleculesDNA-Binding ProteinsEnah protein, humanENA-VASP proteinsMicrofilament ProteinsProlineactinbiochemistrychemical biologyE. coliena/vaspEVH1protein-protein interactionshort linear motif

Identifiers

PMID35076015
PMCPMC8789275
OpenAlexW4205336623

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.