Angiomotins (Amot) are a family of proteins known to have a role in the regulation of cell proliferation, migration, and differentiation. Overexpression of Amot proteins has been shown to induce tumorigenesis, typically in breast cancer tissues. A distinctive feature of Amots is their lipid binding Amot coiled-coil homology (ACCH) domain that exhibits lipid selectivity, particularly with phosphatidylinositols (PI). This interaction with membranes is affiliated with regulating fusion and endocytosis of vesicles carrying polarity proteins and nuclear transcription co-factors known to turn on proliferation & migration pathways.<br/><br/>While the lipid selectivity of the domain has been characterized, the mechanisms involved in its various functions have not been fully described. The current study investigates the role of tyrosine in Amot membrane association. Five nanopeptides with a centrally located tyrosine were synthesized from the Amot sequence, and then characterized for their response to different membrane mimicking environments. We hypothesized that peptides that interact with and are stabilized by the membrane will display blue-shifts to the tyrosine fluorescence peaks. As such, peak shifts in each peptide's absorbance and fluorescence emission spectra were characterized as a function of: 1) alcohol carbon chain lengths and concentration (hydrophobic environment effect), and 2) vesicles with and without PI (amphiphilic environment, charged head group effects). Combined analysis of observed fluorescence and absorbance shifts allows for categorization of the peptides as hydrophobic or hydrophilic region favoring. The results of this work will further our understanding of how these regions of the Amot protein may mediate membrane association and provide potential targets for modulating cancerous function.

Spectral shifts of tyrosine containing ACCH peptides: Insights into Amot function/behavior

ACS Spring Meeting 2021

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