Evidence map›Paper›PMID 27268056›Full record

ArticleThe Journal of biological chemistry2016

Structural Basis of the High Affinity Interaction between the Alphavirus Nonstructural Protein-3 (nsP3) and the SH3 Domain of Amphiphysin-2.

Helena Tossavainen, Olli Aitio, Maarit Hellman, Kalle Saksela, Perttu Permi

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
5.1field-weighted citation impact, top 4% 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

27 citing papers in PubMed, 44 citations in OpenAlex.

  1. Review
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  9. Molecular Virology of Chikungunya Virus.Current topics in microbiology and immunology · 2022
    Review
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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

5 authors at 2 institutions in 1 country.

Helena TossavainenFrom the Program in Structural Biology and Biophysics, Institute of Biotechnology, University of Helsinki and.
Olli AitioFrom the Program in Structural Biology and Biophysics, Institute of Biotechnology, University of Helsinki and.
Maarit HellmanFrom the Program in Structural Biology and Biophysics, Institute of Biotechnology, University of Helsinki and.
Kalle Sakselathe Department of Virology, University of Helsinki and Helsinki University Hospital, FI-00014 Helsinki, Finland and.
Perttu PermiFrom the Program in Structural Biology and Biophysics, Institute of Biotechnology, University of Helsinki and the Departments of Biological and Environmental Science and Chemistry, Nanoscience Center, University of Jyvaskyla, FI-40014 Jyvaskyla, Finland perttu.permi@jyu.fi.
University of Helsinki · FIHelsinki University Hospital · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We show that a peptide from Chikungunya virus nsP3 protein spanning residues 1728-1744 binds the amphiphysin-2 (BIN1) Src homology-3 (SH3) domain with an unusually high affinity (Kd 24 nm). Our NMR solution complex structure together with isothermal titration calorimetry data on several related viral and cellular peptide ligands reveal that this exceptional affinity originates from interactions between multiple basic residues in the target peptide and the extensive negatively charged binding surface of amphiphysin-2 SH3. Remarkably, these arginines show no fixed conformation in the complex structure, indicating that a transient or fluctuating polyelectrostatic interaction accounts for this affinity. Thus, via optimization of such dynamic electrostatic forces, viral peptides have evolved a superior binding affinity for amphiphysin-2 SH3 compared with typical cellular ligands, such as dynamin, thereby enabling hijacking of amphiphysin-2 SH3-regulated host cell processes by these viruses. Moreover, our data show that the previously described consensus sequence PXRPXR for amphiphysin SH3 ligands is inaccurate and instead define it as an extended Class II binding motif PXXPXRpXR, where additional positive charges between the two constant arginine residues can give rise to extraordinary high SH3 binding affinity.

Indexed as

Adaptor Proteins, Signal TransducingAmino Acid MotifsChikungunya virusHumansNuclear Magnetic Resonance, BiomolecularNuclear ProteinsPeptidesProtein Bindingsrc Homology DomainsStatic ElectricityStructure-Activity RelationshipTumor Suppressor ProteinsViral Nonstructural ProteinsAdaptor Proteins, Signal TransducingBIN1 protein, humannsp3 protein, alphavirusNuclear ProteinsPeptidesTumor Suppressor ProteinsViral Nonstructural Proteinsamphiphysin SH3Chikungunya virusdynaminhost-pathogen interactionintrinsically disordered proteinnsP3nuclear magnetic resonance (NMR)protein structureSrc homology 3 domain (SH3 domain)

Identifiers

PMID27268056
PMCPMC4965578
OpenAlexW2412506411

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.