The interactome of the SMRT:GPS2:TBL1:HDAC3 complex

Lead Research Organisation: University of Leicester
Department Name: Sch of Biological Sciences

Abstract

Histone deacetylases (HDACs) are histone modifying enzymes which play a role in a large number of cellular processes, such as protein folding, cell cycle progression, cell signalling and metabolism. The class I HDACs; HDAC1, 2 and 3 all exist in the nucleus as multi protein complexes in which the HDAC activity and specificity is determined by the other components of the complex. The class II HDACs include HDAC4 and 5, and these do not have high intrinsic catalytic activity like the class I HDACs but often operate in complexes together with the class I proteins. This project will involve looking at the interactome of SMRT:GPS2:TBL1:HDAC3 complex to identify key interacting proteins using techniques such as BioID, characterising the interactions and solving the structures of any interactions identified using NMR, crystallography or cryo-EM.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M01116X/1 01/10/2015 30/09/2023
1645549 Studentship BB/M01116X/1 05/10/2015 30/09/2019 Jennifer Gurnett
 
Description A model representing the way the core proteins in the SMRT complex interact has been put together. This consensus model is based on EM data, crosslinking-coupled to mass spectrometry and SAXS.
A range of inositol phosphate derivatives were also tested to analyse the activity of the SMRT complex, this can be used to aid in drug design.
Exploitation Route The model of the core SMRT complex can be used and built upon to uncover more structural and mechanistic details of the SMRT complex binding to nucleosomes and regulating gene expression. The inositol phosphate binding studies can also be used in structure based-drug design to try and design inhibitors to prevent over-activation of the complex in cancers.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description Gramd1 protein structure 
Organisation University of California, Los Angeles (UCLA)
Country United States 
Sector Academic/University 
PI Contribution Structural studies on the Gramd1 proteins
Collaborator Contribution Sent some proteins and materials for structural determination
Impact Progress has been made in structure determination of the Gramd proteins
Start Year 2017
 
Description Inositol phosphates 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution Carried out assays on some provided chemical compounds
Collaborator Contribution Provided chemical compounds
Impact Have elucidated protein activation levels in the presence of a variety of different inositol phosphate compounds
Start Year 2017
 
Description Big Bang Science Fair 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Was standing on a stall with fun activities relating to the work we do in lab at University. Virtual reality headsets with haemoglobin molecules were used as a fun way to look at protein structure, lots of people engaged with this activity and asked questions.
Year(s) Of Engagement Activity 2019
 
Description Brilliant club 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact School tutor teaching aspects of my field, students took an interest and asked lots of questions on the topic, this has hopefully sparked an interest in the sciences.
Year(s) Of Engagement Activity 2017,2018