title: Sequence and structural difference favors a distinct preference of Wnt3a binding with co-receptor LRP6.
abstract: 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.
authors.affiliation: a Stem Cells and Haematological Disorders Laboratory, Department of Biochemistry, School of Life Sciences , University of Hyderabad , (PO) Gachibowli, Hyderabad 500046 , AP , India.
authors.forename: Itishri
authors.initials: I
authors.lastname: Sahu
authors.forename: Seema
authors.initials: S
authors.lastname: Mishra
authors.forename: R
authors.initials: R
authors.lastname: Undi
authors.forename: Ravinder
authors.initials: R
authors.lastname: Kandi
authors.forename: Usha
authors.initials: U
authors.lastname: Gutti
authors.forename: R K
authors.initials: RK
authors.lastname: Gutti
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D006801:Humans; D006860:Hydrogen Bonding; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000737:chemistry*; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D015398:Signal Transduction; D055672:Static Electricity; D040681:Structural Homology, Protein; D013816:Thermodynamics; D051153:Wnt Proteins / Q000737:chemistry*; D060509:Wnt3A Protein / Q000737:chemistry*
chemical_list: C555475:LRP6 protein, human; D060488:Low Density Lipoprotein Receptor-Related Protein-6; C555510:WNT3A protein, human; C435831:WNT5B protein, human; D051153:Wnt Proteins; D060509:Wnt3A Protein
keywords: LRP6; Wnt3a; Wnt5a