Master of Science (MS)
Biochemistry; Biophysics; Chemistry
Intrinsically disordered regions (IDRs) are well known for their conformational flexibility that allows them to engage in a variety of interactions and functions. Compared to structured proteins IDRs have a much larger surface area that is accessible to post-translational modification. These modifications, such as phosphorylation, may conformational changes as they change the surface properties of IDRs. A subset of IDRs, termed molecular recognition features (MoRFs), undergo disorder-to-order transitions in response to a binding partner. α-MoRFs are MoRFs that transition into α-helices in the presence of a binding partner. SIRT1, an NAD+ (nicotinamide adenine dinucleotide)-dependent deacetylase, is notable within the sirtuin family for its large, disordered N- and C-termini, which flank the conserved sirtuin catalytic core. Within the N-terminus lies a region known as Motif A, spanning residues 1-52. The goals of this study were as follows: 1) to examine Motif A binding to SIRT1’s catalytic core using microscale thermophoresis (MST), 2) to determine if Motif A is an α-MoRF using circular dichroism (CD), and 3) to examine how phosphorylation affects Motif A’s binding capability and structural changes via phosphomimetic mutations at Ser27 and Ser47. This project found that Motif A is likely to be an α-MoRF, and that phosphorylation at the previously mentioned phosphorylation sites changes Motif A’s interactions and structural dynamics.
Peralta, Carla Marie, "Elucidating Intramolecular Interactions Within SIRT1 Involving An Intrinsically Disordered Region Of The N-Terminal Domain" (2021). Master's Theses. 5213.
Available for download on Monday, October 26, 2026