Modulation of IL-17 backbone dynamics reduces receptor affinity and reveals a new inhibitory mechanism

Author:

Shaw Daniel J.1ORCID,Waters Lorna C.2,Strong Sarah L.2,Schulze Monika-Sarah E. D.3,Greetham Gregory M.4,Towrie Mike4,Parker Anthony W.4ORCID,Prosser Christine E.3,Henry Alistair J.3,Lawson Alastair D. G.3,Carr Mark. D.2,Taylor Richard J.3,Hunt Neil T.1ORCID,Muskett Frederick W.2ORCID

Affiliation:

1. Department of Chemistry and York Biomedical Research Institute, University of York, Heslington, York, YO19 5DD, UK

2. Department of Molecular and Cell Biology/Leicester Institute of Structural and Chemical Biology, University of Leicester, University Road, Leicester, LE1 7RH, UK

3. UCB Pharma, UCB Biopharma UK, 216 Bath Road, Slough, SL1 3WE, UK

4. Central Laser Facility, Research Complex at Harwell, STFC Rutherford Appleton Laboratory, Harwell Oxford, Didcot, Oxon, OX11 0QX, UK

Abstract

The varying dynamic nature of IL-17 dimers correlates to their affinity for IL-17 receptor A. An inhibitor of IL-17:receptor A binding was shown to rigidify IL-17A revealing an important new regulatory mechanism.

Publisher

Royal Society of Chemistry (RSC)

Subject

General Chemistry

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