ArticleJournal of molecular biology2015
Structures of human CCL18, CCL3, and CCL4 reveal molecular determinants for quaternary structures and sensitivity to insulin-degrading enzyme.
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 20 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
20 citing papers in PubMed, 26 citations in OpenAlex.
- Asthma-mediated control of optic glioma growth via T cell-microglia interactions: A mathematical model.NPJ systems biology and applications · 2026Article
- Factor Analysis-Based Quantitative Endotyping Improves Associations With CRS Cross-Sectional and Longitudinal Outcomes.International forum of allergy & rhinology · 2026Article
- It Takes Two to Tango: Current Understanding of the Role of M16 Family of Proteases and Their Structural Properties.Biomolecules · 2025Review
- Heterodimers Are an Integral Component of Chemokine Signaling Repertoire.International journal of molecular sciences · 2023Review
- Review
- Role of extracellular matrix proteoglycans in immune cell recruitment.International journal of experimental pathology · 2022Review
- Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines.Microbiology spectrum · 2021Article
- Modulation of Insulin Sensitivity by Insulin-Degrading Enzyme.Biomedicines · 2021Review
- Bioinformatics identification of CCL8/21 as potential prognostic biomarkers in breast cancer microenvironment.Bioscience reports · 2020Article
- CCL18 in the Progression of Cancer.International journal of molecular sciences · 2020Review
- Understanding the mechanisms that facilitate specificity, not redundancy, of chemokine-mediated leukocyte recruitment.Immunology · 2020Review
- Discovery of CCL18 antagonist blocking breast cancer metastasis.Clinical & experimental metastasis · 2019Article
- Hepatic Insulin Clearance: Mechanism and Physiology.Physiology (Bethesda, Md.) · 2019Review
- PClass: Protein Quaternary Structure Classification by Using Bootstrapping Strategy as Model Selection.Genes · 2018Article
- Article
- Inositol phosphates and phosphoinositides activate insulin-degrading enzyme, while phosphoinositides also mediate binding to endosomes.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Chemokine CXCL7 Heterodimers: Structural Insights, CXCR2 Receptor Function, and Glycosaminoglycan Interactions.International journal of molecular sciences · 2017Article
- Crystallographic Structure of Truncated CCL21 and the Putative Sulfotyrosine-Binding Site.Biochemistry · 2016Article
- Chemokines and their receptors: insights from molecular modeling and crystallography.Current opinion in pharmacology · 2016Review
- Structural basis for oligomerization and glycosaminoglycan binding of CCL5 and CCL3.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
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 2 institutions in 1 country.
Funding
Abstract
CC chemokine ligands (CCLs) are 8- to 14-kDa signaling proteins involved in diverse immune functions. While CCLs share similar tertiary structures, oligomerization produces highly diverse quaternary structures that protect chemokines from proteolytic degradation and modulate their functions. CCL18 is closely related to CCL3 and CCL4 with respect to both protein sequence and genomic location, yet CCL18 has distinct biochemical and biophysical properties. Here, we report a crystal structure of human CCL18 and its oligomerization states in solution based on crystallographic and small-angle X-ray scattering analyses. Our data show that CCL18 adopts an α-helical conformation at its N-terminus that weakens its dimerization, explaining CCL18's preference for the monomeric state. Multiple contacts between monomers allow CCL18 to reversibly form a unique open-ended oligomer different from those of CCL3, CCL4, and CCL5. Furthermore, these differences hinge on proline 8, which is conserved in CCL3 and CCL4 but is replaced by lysine in human CCL18. Our structural analyses suggest that a mutation of proline 8 to alanine stabilizes a type 1 β-turn at the N-terminus of CCL4 to prevent dimerization but prevents dimers from making key contacts with each other in CCL3. Thus, the P8A mutation induces depolymerization of CCL3 and CCL4 by distinct mechanisms. Finally, we used structural, biochemical, and functional analyses to unravel why insulin-degrading enzyme degrades CCL3 and CCL4 but not CCL18. Our results elucidate the molecular basis for the oligomerization of three closely related CC chemokines and suggest how oligomerization shapes CCL chemokine function.
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.