Biomedical Sciences Research Seminar Series
Signalling with ubiquitin—communication between metabolism and immune responses and DNA damage repair

As part of the School of Science and Technology Biomedical Sciences Research Centre Seminar Series, Dr Elton Zeqiraj, University of Leeds presents: Signalling with ubiquitin—communication between metabolism and immune responses and DNA damage repair.
- From: Wednesday 13 November 2019, 1.10 pm
- To: Wednesday 13 November 2019, 2 pm
- Location: ERD 282, Erasmus Darwin, Nottingham Trent University, Clifton Campus, Clifton Lane, Nottingham, NG11 8NS
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Event details
As part of the School of Science and Technology Biomedical Sciences Research Centre Seminar Series, Dr Elton Zeqiraj, University of Leeds presents: Signalling with ubiquitin—communication between metabolism and immune responses and DNA damage repair.
Abstract
Serine hydroxymethyltransferase 2 (SHMT2) regulates one-carbon transfer reactions that are essential for amino acid and nucleotide metabolism, and uses pyridoxal-5'-phosphate (PLP) as a cofactor. Apo SHMT2 exists as a dimer with unknown functions, whereas PLP binding stabilizes the active tetrameric state. SHMT2 also promotes inflammatory cytokine signalling by interacting with the deubiquitylating BRCC36 isopeptidase complex (BRISC), although it is unclear whether this function relates to metabolism. Here we present the cryo-electron microscopy structure of the human BRISC-SHMT2 complex at a resolution of 3.8 Å. BRISC is a U-shaped dimer of four subunits, and SHMT2 sterically blocks the BRCC36 active site and inhibits deubiquitylase activity. Only the inactive SHMT2 dimer-and not the active PLP-bound tetramer-binds and inhibits BRISC. Mutations in BRISC that disrupt SHMT2 binding impair type I interferon signalling in response to inflammatory stimuli. Intracellular levels of PLP regulate the interaction between BRISC and SHMT2, as well as inflammatory cytokine responses. These data reveal a mechanism in which metabolites regulate deubiquitylase activity and inflammatory signalling.
Hosted by Yasser El-Sherbiny
All welcome.
For any enquiries please contact Dr Amanda Coutts
Location details
Room/Building:
Address:
Clifton Campus
Clifton Lane
Nottingham
NG11 8NS
Past event