Comprehensive In Silico Analysis of the CXCL12, C55Y Mutation Reveals Structural and Functional Disruption in
Shah Kamal1,2,3, Najeeb Ullah4, Yanjuan Wang1,2,3
1School of Traditional Chinese Medicine, Faculty of Medicine, Yangzhou University, Yangzhou, Jiangsu, China.
Evolutionary Bioinformatics Online
|August 7, 2026
Summary
The C55Y mutation destabilizes CXCL12, impairing its binding to CXCR4 and CXCR7 receptors. This disruption affects prostate cancer metastasis and immune response, offering new therapeutic targets.
Area of Science:
- Molecular biology
- Biochemistry
- Computational biology
Background:
- Chemokine CXCL12 (C-X-C motif chemokine ligand 12) is crucial for immune cell movement and cancer spread via CXCR4 and CXCR7 receptors.
- The C55Y mutation in CXCL12 is hypothesized to uniquely destabilize its structure by affecting a key disulfide bond.
Purpose of the Study:
- To investigate the structural and functional consequences of the CXCL12 C55Y mutation.
- To evaluate its impact on CXCR4 and CXCR7 interactions and relevance to prostate cancer.
Main Methods:
- Molecular dynamics simulations (MDS) and evolutionary conservation analysis were employed.
- Protein stability was assessed using I-TASSER, Meta-SNP, and PolyPhen-2.
- Receptor binding was analyzed via HDOCK, Schrödinger simulations, RMSD, and RMSF calculations.
Main Results:
- The C55Y mutation caused significant structural instability and altered secondary structure in CXCL12.
- MDS revealed reduced structural compactness compared to normal CXCL12 complexes.
- Docking studies indicated decreased binding affinity to both CXCR4 and CXCR7, unlike other mutations.
Conclusions:
- The C55Y mutation disrupts CXCL12 structure and function, compromising both CXCR4 and CXCR7 pathways.
- This unique dual-receptor binding loss suggests a distinct role in prostate cancer progression.
- Findings offer insights for developing targeted therapies against CXCL12 signaling in prostate cancer.
