Akademik Veri Yönetim Sistemi
HIBIT2024 (17th International HIBIT Conference), İstanbul, Türkiye, 18 - 20 Aralık 2024, ss.85, (Özet Bildiri)
Obesity affects over half a billion individuals worldwide and is influenced by both genetic and environmental factors. In our previous study involving a Turkish cohort, we identified the Six-Transmembrane Epithelial Antigen Protein 1B (STEAP1B) gene as associated with obesity, uncovering seven mutations through family segregation analysis. The STEAP protein family, known for its roles in metal ion transport and redox reactions, is crucial in cellular metabolism and cancer progression. Given STEAP1B's structural similarities to STEAP1 and the limited understanding of its function and membrane assembly, we aimed to predict key molecular interactions and conformational changes related to its pathogenic role in obesity.
In this study, we applied structural bioinformatics and molecular dynamics (MD) simulations—the first time for STEAP1B—to investigate its structural and functional characteristics. Using AlphaFold-based modeling and MD simulations, we examined the wild-type (WT) STEAP1B protein and five missense variants. Analysis of MD trajectories for the apo form of membrane-embedded STEAP1B monomers revealed that variants with single-nucleotide polymorphisms (SNPs), Q163R and L257P exhibited slight structural alterations, suggesting potential functional implications in obesity. We further modeled and simulated the WT and these two variants in homotrimeric structures bound to heme and flavin adenine dinucleotide (FAD) ligands, providing initial insights into possible membrane-embedded assembly forms of STEAP1B. The results of our study provide new insights into the homotrimeric structure of STEAP1B and its obesity-associated variants, particularly Q163R and L257P.