ArticleACS chemical biology2013
Sulfopeptide probes of the CXCR4/CXCL12 interface reveal oligomer-specific contacts and chemokine allostery.
Article in ACS chemical biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 55 citations in OpenAlex.
- Chemical Strategies for Controlling Sulfation in Biomacromolecules.ACS chemical biology · 2026Review
- CXCL12 chemokine dimer signaling modulates acute myelogenous leukemia cell migration through altered receptor internalization.Scientific reports · 2025Article
- Encoding and decoding selectivity and promiscuity in the human chemokine-GPCR interaction network.Cell · 2025Article
- The acidic intrinsically disordered region of the inflammatory mediator HMGB1 mediates fuzzy interactions with CXCL12.Nature communications · 2024Article
- Fragment-based drug discovery of small molecule ligands for the human chemokine CCL28.SLAS discovery : advancing life sciences R & D · 2023Article
- Co-translational Installation of Posttranslational Modifications by Non-canonical Amino Acid Mutagenesis.Chembiochem : a European journal of chemical biology · 2023Article
- Studying Protein Tyrosine O-Sulfation in Mammalian Cells with Genetically Encoded Sulfotyrosine.Current protocols · 2021Article
- The dimeric form of CXCL12 binds to atypical chemokine receptor 1.Science signaling · 2021Article
- Functional genetic encoding of sulfotyrosine in mammalian cells.Nature communications · 2020Article
- Functional anatomy of the full-length CXCR4-CXCL12 complex systematically dissected by quantitative model-guided mutagenesis.Science signaling · 2020Article
- Discovery of 5,5'-Methylenedi-2,3-Cresotic Acid as a Potent Inhibitor of the Chemotactic Activity of the HMGB1·CXCL12 Heterocomplex Using Virtual Screening and NMR Validation.Frontiers in chemistry · 2020Article
- Diflunisal targets the HMGB1/CXCL12 heterocomplex and blocks immune cell recruitment.EMBO reports · 2019Article
- WHIM Syndrome: from Pathogenesis Towards Personalized Medicine and Cure.Journal of clinical immunology · 2019Review
- The Solution Structure of CCL28 Reveals Structural Lability that Does Not Constrain Antifungal Activity.Journal of molecular biology · 2018Article
- Identification of an Arg-Leu-Arg tripeptide that contributes to the binding interface between the cytokine MIF and the chemokine receptor CXCR4.Scientific reports · 2018Article
- Detecting Cell Surface Expression of the G Protein-Coupled Receptor CXCR4.Methods in molecular biology (Clifton, N.J.) · 2018Article
- Differences in Sulfotyrosine Binding amongst CXCR1 and CXCR2 Chemokine Ligands.International journal of molecular sciences · 2017Article
- Enriching Traditional Protein-protein Interaction Networks with Alternative Conformations of Proteins.Scientific reports · 2017Article
- Fluorescent CXCR4 targeting peptide as alternative for antibody staining in Ewing sarcoma.BMC cancer · 2017Article
- What Do Structures Tell Us About Chemokine Receptor Function and Antagonism?Annual review of biophysics · 2017Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Tyrosine sulfation is a post-translational modification that enhances protein-protein interactions and may identify druggable sites in the extracellular space. The G protein-coupled receptor CXCR4 is a prototypical example with three potential sulfation sites at positions 7, 12, and 21. Each receptor sulfotyrosine participates in specific contacts with its chemokine ligand in the structure of a soluble, dimeric CXCL12:CXCR4(1-38) complex, but their relative importance for CXCR4 binding and activation by the monomeric chemokine remains undefined. NMR titrations with short sulfopeptides showed that the tyrosine motifs of CXCR4 varied widely in their contributions to CXCL12 binding affinity and site specificity. Whereas the Tyr21 sulfopeptide bound the same site as in previously solved structures, the Tyr7 and Tyr12 sulfopeptides interacted nonspecifically. Surprisingly, the unsulfated Tyr7 peptide occupied a hydrophobic site on the CXCL12 monomer that is inaccessible in the CXCL12 dimer. Functional analysis of CXCR4 mutants validated the relative importance of individual CXCR4 sulfotyrosine modifications (Tyr21 > Tyr12 > Tyr7) for CXCL12 binding and receptor activation. Biophysical measurements also revealed a cooperative relationship between sulfopeptide binding at the Tyr21 site and CXCL12 dimerization, the first example of allosteric behavior in a chemokine. Future ligands that occupy the sTyr21 recognition site may act as both competitive inhibitors of receptor binding and allosteric modulators of chemokine function. Together, our data suggests that sulfation does not ubiquitously enhance complex affinity and that distinct patterns of tyrosine sulfation could encode oligomer selectivity, implying another layer of regulation for chemokine signaling.
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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.