RESUMEN

Wnt signaling pathway plays a key role in a wide array of development and physiological processes. Wnt proteins interact with two different co-receptors LRP5/6 and ROR 2, leading to different signal transductions in the cell. Though the Wnt family of proteins has high sequence similarity the specificity for particular co-receptor is not well understood. The choice of pathway is attributed to the binding of Wnt complex to the co-receptor. Our current study is a novel approach using homology modeling, docking, and structural alignment to unravel the structural differences between Wnt3a and Wnt5b binding to LRP6. The conservation of a protruding loop has been identified in Wnt3a protein indicating an enhanced ability of Wnt3a to bind to LRP5/6 against its counter parts. The docking studies have further substantiated the findings. This could potentially help us design and develop novel inhibitors targeting Wnt3a-LRP6 complex in specific tissues or disease states.

Asunto(s)

Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad/química , Simulación del Acoplamiento Molecular , Proteínas Wnt/química , Proteína Wnt3A/química , Secuencia de Aminoácidos , Animales , Sitios de Unión , Humanos , Enlace de Hidrógeno , Datos de Secuencia Molecular , Unión Proteica , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Alineación de Secuencia , Transducción de Señal , Electricidad Estática , Homología Estructural de Proteína , Termodinámica