Open Access. Powered by Scholars. Published by Universities.®
Public Health Education and Promotion Commons™
Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 2 of 2
Full-Text Articles in Public Health Education and Promotion
Structural Insights Into The Disruption Of Tnf-Tnfr1 Signalling By Small Molecules Stabilising A Distorted Tnf, David Mcmillan, Carlos Martinez-Fleites, John Porter, David Fox, Rachel E. Davis, Prashant Mori, Tom Ceska, Bruce Carrington, Alastair Lawson, Tim Bourne, James O'Connell
Structural Insights Into The Disruption Of Tnf-Tnfr1 Signalling By Small Molecules Stabilising A Distorted Tnf, David Mcmillan, Carlos Martinez-Fleites, John Porter, David Fox, Rachel E. Davis, Prashant Mori, Tom Ceska, Bruce Carrington, Alastair Lawson, Tim Bourne, James O'Connell
Faculty Publications
Tumour necrosis factor (TNF) is a trimeric protein which signals through two membrane receptors, TNFR1 and TNFR2. Previously, we identified small molecules that inhibit human TNF by stabilising a distorted trimer and reduce the number of receptors bound to TNF from three to two. Here we present a biochemical and structural characterisation of the small molecule-stabilised TNF-TNFR1 complex, providing insights into how a distorted TNF trimer can alter signalling function. We demonstrate that the inhibitors reduce the binding affinity of TNF to the third TNFR1 molecule. In support of this, we show by X-ray crystallography that the inhibitor-bound, distorted, TNF …
Megf10 Deficiency Impairs Skeletal Muscle Stem Cell Migration And Muscle Regeneration, Chengcheng Li, Dorianmarie Vargas-Franco, Madhurima Saha, Rachel M. Davis, Kelsey A. Manko, Isabelle Draper, Christina A. Pacak, Peter B. Kang
Megf10 Deficiency Impairs Skeletal Muscle Stem Cell Migration And Muscle Regeneration, Chengcheng Li, Dorianmarie Vargas-Franco, Madhurima Saha, Rachel M. Davis, Kelsey A. Manko, Isabelle Draper, Christina A. Pacak, Peter B. Kang
Faculty Publications
Biallelic loss-of-function MEGF10 mutations lead to MEGF10 myopathy, also known as early onset myopathy with areflexia, respiratory distress, and dysphagia (EMARDD). MEGF10 is expressed in muscle satellite cells, but the contribution of satellite cell dysfunction to MEGF10 myopathy is unclear. Myofibers and satellite cells were isolated and examined from Megf10 and wild-type mice. A separate set of mice underwent repeated intramuscular barium chloride injections. Megf10 muscle satellite cells showed reduced proliferation and migration, while Megf10 mouse skeletal muscles showed impaired regeneration. Megf10 deficiency is associated with impaired muscle regeneration, due in part to defects in satellite cell function. Efforts to …