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
Wang ZA
(2020)
Diverse nucleosome Site-Selectivity among histone deacetylase complexes.
in eLife
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M01116X/1 | 01/10/2015 | 31/03/2024 | |||
| 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 | The Cholesterol Constellation |
| Amount | $6,000,000 (USD) |
| Organisation | The Leducq Foundation |
| Sector | Charity/Non Profit |
| Country | France |
| Start | 01/2020 |
| End | 12/2024 |
| Description | Aster-A protein structure |
| Organisation | University of California, Los Angeles (UCLA) |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Structural studies on the Aster-A proteins |
| Collaborator Contribution | Sent us some proteins and materials for structural determination, which with the biology they were doing built up a story of the role of these proteins. |
| Impact | Progress has been made in structure determination of the Aster proteins and a paper was published on this. |
| 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 |