Publications by authors named "Matthew Holly"
Article Synopsis
- Researchers utilized cryo-electron microscopy (cryo-EM) to determine the full-length structure of the thyroid-stimulating hormone receptor (TSHR) complexed with a human monoclonal autoantibody K1-70™, a potent inhibitor of TSH action.
- The TSHR was found to have a monomeric structure, displaying three domains: the leucine-rich domain (LRD), hinge region (HR), and transmembrane domain (TMD), with noticeable interactions between the TMD and the extracellular domain (ECD) that explain the effects of TSHR mutations.
- The study also highlights how the binding of another stimulating autoantibody, M22™, may require the HR to rotate upwards to avoid cl
The crystal structures of the thyroid-stimulating hormone receptor (TSHR) leucine-rich repeat domain (amino acids 22-260; TSHR260) in complex with a stimulating human monoclonal autoantibody (M22TM) and in complex with a blocking human autoantibody (K1-70™) have been solved. However, attempts to purify and crystallise free TSHR260, that is not bound to an autoantibody, have been unsuccessful due to the poor stability of free TSHR260. We now describe a TSHR260 mutant that has been stabilised by the introduction of six mutations (H63C, R112P, D143P, D151E, V169R and I253R) to form TSHR260-JMG55TM, which is approximately 900 times more thermostable than wild-type TSHR260.
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