1. Ab initio protein modelling reveals novel human MIT domains
- Author
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Daniel J. Rigden, Sebastian D. Hayes, Sylvie Urbé, Michael J. Clague, and Han Liu
- Subjects
Models, Molecular ,Microtubule interacting and transport ,Protein family ,Molecular Sequence Data ,Biophysics ,Ab initio ,Gene Expression ,Protein modelling ,Charged multivesicular body protein ,Computational biology ,Microtubules ,Biochemistry ,Homologous Sequences ,Ubiquitin ,Structural Biology ,Microtubule ,Databases, Genetic ,Hydrolase ,Genetics ,Humans ,Computer Simulation ,Amino Acid Sequence ,Molecular Biology ,Sequence Homology, Amino Acid ,Ab initio protein structure modelling ,biology ,Computational Biology ,Proteins ,Biological Transport ,Cell Biology ,Database searching ,Protein Structure, Tertiary ,Profile–profile matching ,Crystallography ,biology.protein ,Sequence Alignment - Abstract
Database searches can fail to detect all truly homologous sequences, particularly when dealing with short, highly sequence diverse protein families. Here, using microtubule interacting and transport (MIT) domains as an example, we have applied an approach of profile–profile matching followed by ab initio structure modelling to the detection of true homologues in the borderline significant zone of database searches. Novel MIT domains were confidently identified in USP54, containing an apparently inactive ubiquitin carboxyl-terminal hydrolase domain, a katanin-like ATPase KATNAL1, and an uncharacterized protein containing a VPS9 domain. As a proof of principle, we have confirmed the novel MIT annotation for USP54 by in vitro profiling of binding to CHMP proteins.Structured summaryUSP8 binds:CHMPs 1A 1B 2A 2B 4CUSP54 binds:CHMPs 1B 2A 2B 4C 6
- Published
- 2009
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