ArticleBiochemistry2009
SH3 domains of Grb2 adaptor bind to PXpsiPXR motifs within the Sos1 nucleotide exchange factor in a discriminate manner.
Article in Biochemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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.
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.
Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- Development and Recent Advances in SLIPT-PM: A Chemogenetic Platform for Manipulating Signaling at the Plasma Membrane.Chembiochem : a European journal of chemical biology · 2025Review
- Conserved proline residues prevent dimerization and aggregation in the β-lactamase BlaC.Protein science : a publication of the Protein Society · 2024Article
- The Configuration of GRB2 in Protein Interaction and Signal Transduction.Biomolecules · 2024Review
- Functional Classification and Interaction Selectivity Landscape of the Human SH3 Domain Superfamily.Cells · 2024Article
- Allosteric regulation of GRB2 modulates RAS activation.Small GTPases · 2022Article
- SOS1 interacts with Grb2 through regions that induce closed nSH3 conformations.The Journal of chemical physics · 2020Article
- Rapid Quantification of Protein-Ligand Binding viaBiophysical journal · 2020Article
- High-Affinity Interactions of the nSH3/cSH3 Domains of Grb2 with the C-Terminal Proline-Rich Domain of SOS1.Journal of the American Chemical Society · 2020Article
- Allosteric KRas4B Can Modulate SOS1 Fast and Slow Ras Activation Cycles.Biophysical journal · 2018Article
- Article
- Binding Mechanism of the N-Terminal SH3 Domain of CrkII and Proline-Rich Motifs in cAbl.Biophysical journal · 2016Article
- Regions outside of conserved PxxPxR motifs drive the high affinity interaction of GRB2 with SH3 domain ligands.Biochimica et biophysica acta · 2015Article
- The proline-rich region of 18.5 kDa myelin basic protein binds to the SH3-domain of Fyn tyrosine kinase with the aid of an upstream segment to form a dynamic complex in vitro.Bioscience reports · 2014Article
- Allostery mediates ligand binding to Grb2 adaptor in a mutually exclusive manner.Journal of molecular recognition : JMR · 2013Article
- Article
- Grb2, a double-edged sword of receptor tyrosine kinase signaling.Science signaling · 2012Review
- Multivalent binding and facilitated diffusion account for the formation of the Grb2-Sos1 signaling complex in a cooperative manner.Biochemistry · 2012Article
- Arginine mimetics using α-guanidino acids: introduction of functional groups and stereochemistry adjacent to recognition guanidiniums in peptides.Chembiochem : a European journal of chemical biology · 2012Article
- Proline substitutions and threonine pseudophosphorylation of the SH3 ligand of 18.5-kDa myelin basic protein decrease its affinity for the Fyn-SH3 domain and alter process development and protein localization in oligodendrocytes.Journal of neuroscience research · 2012Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Ubiquitously encountered in a wide variety of cellular processes, the Grb2-Sos1 interaction is mediated through the combinatorial binding of nSH3 and cSH3 domains of Grb2 to various sites containing PXpsiPXR motifs within Sos1. Here, using isothermal titration calorimetry, we demonstrate that while the nSH3 domain binds with affinities in the physiological range to all four sites containing PXpsiPXR motifs, designated S1, S2, S3, and S4, the cSH3 domain can only do so at the S1 site. Further scrutiny of these sites yields rationale for the recognition of various PXpsiPXR motifs by the SH3 domains in a discriminate manner. Unlike the PXpsiPXR motifs at S2, S3, and S4 sites, the PXpsiPXR motif at the S1 site is flanked at its C-terminus with two additional arginine residues that are absolutely required for high-affinity binding of the cSH3 domain. In striking contrast, these two additional arginine residues augment the binding of the nSH3 domain to the S1 site, but their role is not critical for the recognition of S2, S3, and S4 sites. Site-directed mutagenesis suggests that the two additional arginine residues flanking the PXpsiPXR motif at the S1 site contribute to free energy of binding via the formation of salt bridges with specific acidic residues in SH3 domains. Molecular modeling is employed to project these novel findings into the 3D structures of SH3 domains in complex with a peptide containing the PXpsiPXR motif and flanking arginine residues at the S1 site. Taken together, this study furthers our understanding of the assembly of a key signaling complex central to cellular machinery.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.