Abstract
Atopic dermatitis (AD) is the most prevalent chronic inflammatory skin condition globally, and many patients do not respond adequately to currently available therapies [1]. Interleukin-22 receptor 1 (IL-22RA1) has been identified as a potential mediator of AD, but no treatments for this pathway are currently on the market [2]. In this work, we aim to elucidate the biophysics of the binary and ternary IL-22RA1 complex formation with interleukins by combining surface plasmon resonance requiring protein immobilization and in-solution techniques such as small angle X-ray scattering and circular dichroism. In addition, structural characterization of the ternary complexes by high-resolution cryogenic electron microscopy is ongoing and will be used to provide Angstrom resolution structural data about the complexes. This will be coupled to molecular dynamics simulations, providing a comprehensive overview of the formation of IL-22RA1 signaling complexes resulting in knowledge on the domains involved in the signaling process. This will result in new and novel knowledge on the interaction with these interleukins and IL22R1 and provide insights into the role of these interleukins and potential approaches to block their interaction by an antibody approach.
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