Sequence and structural difference favors a distinct preference of Wnt3a binding with co-receptor LRP6 |
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Authors: | Itishri Sahu Seema Mishra R. Undi Ravinder Kandi Usha Gutti |
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Affiliation: | 1. Stem Cells and Haematological Disorders Laboratory, Department of Biochemistry, School of Life Sciences, University of Hyderabad, (PO) Gachibowli, Hyderabad 500046, AP, India https://orcid.org/0000-0002-6069-656X;2. Bioinformatics and Systems Biology Laboratory, Department of Biochemistry, School of Life Sciences, University of Hyderabad, (PO) Gachibowli, Hyderabad 500046, AP, India;3. Stem Cells and Haematological Disorders Laboratory, Department of Biochemistry, School of Life Sciences, University of Hyderabad, (PO) Gachibowli, Hyderabad 500046, AP, India;4. Stem Cells and Haematological Disorders Laboratory, Department of Biochemistry, School of Life Sciences, University of Hyderabad, (PO) Gachibowli, Hyderabad 500046, AP, India https://orcid.org/0000-0002-2875-8046;5. Department of Biotechnology, GITAM Institute of Science, GITAM University, Visakhapatnam 530 045, AP, India |
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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. |
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Keywords: | Wnt3a Wnt5a LRP6 |
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