Evidence mapPaperPMID 42564356Full record

ArticleEvolutionary bioinformatics online2026

Comprehensive In Silico Analysis of the CXCL12, C55Y Mutation Reveals Structural and Functional Disruption in CXCR4/CXCR7 Signaling.

Shah Kamal, Najeeb Ullah, Yanjuan Wang, Chen Qin, Ruilin He, Habib Ullah, Mariam Ahmed Mujtaba, Amanullah Amanullah, Kashif Ali Khan, Mohammad Amjad Kamal and 1 more

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Article in Evolutionary bioinformatics online, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Shah KamalSchool of Traditional Chinese Medicine, Faculty of Medicine, Yangzhou University, Yangzhou, Jiangsu, China.ORCID https://orcid.org/0000-0001-9218-2929
Najeeb UllahJiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China.
Yanjuan WangSchool of Traditional Chinese Medicine, Faculty of Medicine, Yangzhou University, Yangzhou, Jiangsu, China.
Chen QinSchool of Traditional Chinese Medicine, Faculty of Medicine, Yangzhou University, Yangzhou, Jiangsu, China.
Ruilin HeSchool of Traditional Chinese Medicine, Faculty of Medicine, Yangzhou University, Yangzhou, Jiangsu, China.
Habib UllahJoint International Research Laboratory of Agriculture and Agri-Product Safety, Jiangsu Key Laboratory of Crop Genomics and Molecular Breeding, The Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, China.
Mariam Ahmed MujtabaDepartment of Biotechnology, Women University Mardan, East Canal Road, Mardan, Pakistan.
Amanullah AmanullahJiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China.
Kashif Ali KhanDepartment of Pharmacy, Shaheed Benazir Bhutto University, Shringal, Dir Upper, Pakistan.
Mohammad Amjad KamalFuture Technologies Research Centre, King Faisal University, Al Ahsa, Saudi Arabia.
Wenji LiSchool of Traditional Chinese Medicine, Faculty of Medicine, Yangzhou University, Yangzhou, Jiangsu, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: CXCL12 is a critical chemokine involved in immune cell trafficking and tumor metastasis through its interaction with CXCR4 and CXCR7. The C55Y mutation in CXCL12 is hypothesized to disrupt its structure and function. Unlike previously reported CXCL12 mutations that affect transcriptional regulation or single-receptor binding, C55Y targets a conserved cysteine residue essential for a structural disulfide bridge, potentially inducing unique global destabilization. This study investigates the molecular consequences of the C55Y mutation using computational tools. Objectives: This study aimed to evaluate the structural and functional impact of the C55Y mutation in CXCL12, particularly its interactions with CXCR4 and CXCR7, and its relevance to prostate cancer pathogenesis. Methods: Molecular dynamics simulations (MDS), evolutionary conservation analysis, and molecular docking with CXCR4 and CXCR7 receptors were performed to assess the impact of the C55Y mutation. Tools such as I-TASSER, Meta-SNP, and PolyPhen-2 were used to analyze structural stability, while HDOCK and Schrödinger simulations assessed receptor binding. RMSD and RMSF calculations were used to evaluate protein dynamics. Results: The C55Y mutation induces significant structural instability in CXCL12, with increased RMSD and altered secondary structure. Molecular dynamics simulation further demonstrated the stability of the complexes through RMSD, RMSF, hydrogen bond, and Radius of Gyration (RoG) analyses, where the normal complexes exhibited comparatively stable structural compactness during the simulation period. Docking studies showed reduced binding affinity to CXCR4 and CXCR7, indicating disrupted receptor interactions. Notably, this dual-receptor binding loss distinguishes C55Y from other mutations that typically impair only CXCR4 signaling. These findings suggest that the mutation impairs CXCL12's function in prostate cancer, metastasis of prostate cancer, and immune response. Conclusion: The C55Y mutation in CXCL12 disrupts its structural integrity and receptor binding, uniquely compromising both the CXCR4 and CXCR7 pathways. This highlights its potential role in prostate cancer progression through mechanisms distinct from previously characterized CXCL12 variants. This study provides insights into the molecular mechanisms of CXCL12-mediated signaling and its implications for future therapeutic strategies targeting chemokine signaling to inhibit prostate cancer.

Indexed as

C55Y mutationCXCL12dockingmolecular dynamics simulationsprostate cancerreceptor binding

Identifiers

PMID42564356
PMCPMC13443258

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