Researcher ORCID Identifier
0000-0001-9992-3646
Graduation Year
2022
Date of Submission
4-2022
Document Type
Campus Only Senior Thesis
Degree Name
Bachelor of Arts
Department
Biochemistry
Reader 1
Ethan van Arnam
Reader 2
Bethany Caulkins
Terms of Use & License Information
Rights Information
© 2022 Andrew J Maltz
Abstract
One of biology’s most important post-translational protein modifications, the process of protein lipidation confers a host of conformational and functional changes. While the most documented function involves enhanced membrane association, the full breadth of this modification’s capabilities has yet to be fully understood. Specifically, attempts to document a comprehensive list of proteins that undergo myristoylation, or the addition of the 14-carbon-long myristic acid, always seem to remain incomplete; the constant discovery of existing proteins being targeted by this cotranslational constantly requires us to strengthen our understanding of the target protein’s necessary peptide motifs required for N-myristoyltransferase (NMT) association. To properly understand the magnitude of this modification across the global proteome and gain insight into the vast functionality of this modification, an accurate way to identify myristoylation targets on proteins must be developed. To this end, this proposal seeks to explore the currently accepted consensus motif and develop a method based on mass spectrometry to accurately analyze the addition of native myristic acid to predicted targets. If this methodology can detect and quantify degrees of myristoylation in novel proteins targets as predicted, it will provide a cost-effective and time-efficient way of detecting myristoylation and give valuable insight into the selectivity of NMT. We first aim to detect myristoylation in the mass spectra of two proteins established to undergo this modification, specifically p60src from the Src family of proteins and the p15 domain of BID from the Bcl-2 family. We then look to swapping the extended consensus motifs of these two proteins, as well as adding this consensus motif to a non-modifiable protein and comparing the mass spectra to quantify selectivity and confirm this method’s effectiveness. If successful, this experiment could not only provide a broadly applicable methodology to quantify modifications on functional proteins, but it may further elucidate the amino acids necessary to be considered a target for myristyolation.
Recommended Citation
Maltz, Andrew, "Investigating and Expanding the N-myristoyltransferase Consensus Motif in Src and BID Family Proteins" (2022). CMC Senior Theses. 3015.
https://scholarship.claremont.edu/cmc_theses/3015
This thesis is restricted to the Claremont Colleges current faculty, students, and staff.
