CytoSIP: an annotated structural atlas for interactions involving cytokines or cytokine receptors

Area of Science:

• Biochemistry and structural biology
• Genomics and bioinformatics
• Drug discovery and precision medicine

Background:

• Cytokine-cytokine receptor (CK-CKR) interactions are crucial in cellular signaling and disease, including cancer.
• Targeting CK-CKR interactions offers therapeutic potential, but a lack of structural data hinders drug development.
• Developing structure-driven therapeutics requires accessible, annotated surface regions of CK-CKR complexes.

Purpose of the Study:

• To develop CytoSIP, a novel rich internet application and database for investigating CK-CKR interactions.
• To provide a comprehensive resource linking genetic variants (SNPs), protein interfaces, and disease phenotypes.
• To facilitate structure-driven drug discovery for CK-CKR related pathologies.

Main Methods:

• Creation of a database integrating Single nucleotide polymorphisms (SNPs), Interface data, and Phenotypes (SIP) for CK-CKR.
• Development of a tri-level SIP data model connecting genetic variants, protein structures, and disease phenotypes.
• Implementation of customized screening tools for analyzing CK-CKR surface hotspots and associated pathologies.

Main Results:

• CytoSIP provides atomic interaction data for experimentally determined CK-CKR structural complexes.
• The database includes SNPs, CK-CKR domains, interfaces, epitopes, and associated diseases/phenotypes.
• Customized tools enable efficient interrogation of large datasets, reducing research time and resources.

Conclusions:

• CytoSIP bridges the gap between genetic variations and disease phenotypes through protein structure analysis.
• The accessible portal facilitates the investigation of CK-CKR crosstalk for targeted therapeutic agent development.
• This resource supports precision medicine by enabling a panoramic view of CK-CKR interactions and their pathological relevance.