Full metadata
Title
Discovery and characterization of a potential human AMPylator
Description
Protein AMPylation is a recently discovered and relatively unstudied post-translational modification (PTM). AMPylation has previously been shown to play an important role in metabolic regulation and host pathogenesis in bacteria, but the recent identification of potential AMPylators across many species in every domain of life has supported the possibility that AMPylation could be a more fundamental and physiologically significant regulatory PTM. For the first time, we characterized the auto-AMPylation capability of the human protein SOS1 through in vitro AMPylation experiments using full-length protein and whole-domain truncation mutants. We found that SOS1 can become AMPylated at a tyrosine residue possibly within the Cdc25 domain of the protein, the Dbl homology domain is vital for efficient auto-AMPylation activity, and the C-terminal proline-rich domain exhibits a complex regulatory function. The proline-rich domain alone also appears to be capable of catalyzing a separate, unidentified covalent self-modification using a fluorescent ATP analogue. Finally, SOS1 was shown to be capable of catalyzing the AMPylation of two endogenous human protein substrates: a ubiquitous, unidentified protein of ~49kDa and another breast-cancer specific, unidentified protein of ~28kDa.
Date Created
2014-05
Contributors
- Ober-Reynolds, Benjamin John (Author)
- LaBaer, Joshua (Thesis director)
- Borges, Chad (Committee member)
- Barrett, The Honors College (Contributor)
- Department of Chemistry and Biochemistry (Contributor)
- School of Life Sciences (Contributor)
Topical Subject
Resource Type
Extent
34 pages
Language
Copyright Statement
In Copyright
Primary Member of
Series
Academic Year 2013-2014
Handle
https://hdl.handle.net/2286/R.I.22606
Level of coding
minimal
Cataloging Standards
System Created
- 2017-10-30 02:50:57
System Modified
- 2021-08-11 04:09:57
- 2 years 9 months ago
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