Preliminary investigation of caspase6 cleavage of HTT and HTT-HAP40 2019/07/15
| Main Authors: | Harding, Rachel, Arrowsmith, Cheryl, Edwards, Aled |
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| Format: | info dataset |
| Terbitan: |
, 2019
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| Subjects: | |
| Online Access: |
https://zenodo.org/record/3382319 |
Daftar Isi:
- Project: Structural and functional analysis of huntingtin protein Experiment: Preliminary investigation of caspase6 cleavage of HTT and HTT-HAP40 Date: 2019/07/15 Background: HTT is cleaved by numerous enzymes to generate protein fragments, many of which have implications for disease pathogenesis (reviewed by Saudou et al (2016) Neuron). However, very few of these proteases have been assessed for their cleavage of purified HTT protein or HTT-HAP40 protein samples. Caspase-6 cleavage of HTT has been reported to generate a aa. 1-586 fragment. However, it is not clear how HAP40 binding of HTT might affect cleavage by caspase-6 or release of this fragment from the complex structure. The caspase-6 cleavage site is in the intrinsically disordered region, distal from the globular structure. How cleavage might release a 1-586 fragment from the remainder of the structure remains incompletely understood. Rationale: In this experiments I am aiming to optimise conditions for caspase-6 cleavage to test how proteolytic cleavage of HTT affects “pathogenic” fragment formation for apo vs HAP40-bound HTT.
- Dr. Harding is the recipient of the Huntington's Disease Society of America Berman Topper Career Development Fellowship which funds and supports this research, in addition to generous funding from the CHDI Foundation and the Huntington Society of Canada. The SGC is a registered charity (number 1097737) that receives funds from AbbVie, Bayer Pharma AG, Boehringer Ingelheim, Canada Foundation for Innovation, Eshelman Institute for Innovation, Genome Canada through Ontario Genomics Institute [OGI-055], Innovative Medicines Initiative (EU/EFPIA) [ULTRA-DD grant no. 115766], Janssen, Merck KGaA, Darmstadt, Germany, MSD, Novartis Pharma AG, Ontario Ministry of Research, Innovation and Science (MRIS), Pfizer, São Paulo Research Foundation-FAPESP, Takeda, and Wellcome.