Sequence-Based Properties that Identify Intrinsically Disordered Phase-Separating Protein Regions

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dc.contributor.advisorLewis, Karen A.
dc.contributor.advisorWhitten, Steven T.
dc.contributor.authorIbrahim, Ayyam
dc.contributor.committeeMemberLewis, L. Kevin
dc.contributor.committeeMemberXue, Xiaoyu
dc.date.accessioned2022-09-06T13:32:29Z
dc.date.available2022-09-06T13:32:29Z
dc.date.issued2022-08
dc.description.abstractWe aimed to investigate the molecular mechanisms that drive liquid-liquid phase separation (LLPS) of intrinsically disordered proteins (IDPs). This phenomenon is critical in many cellular processes (including RNA metabolism, chromatin rearrangement, and signal transduction), and known to be driven primarily, but not exclusively, by IDPs. To fully understand how these processes occur and are regulated, it is important that we understand the interactions and sequence properties underlying phase separation behavior. IDPs are proteins that contain intrinsically disordered regions (IDRs), which are regions that do not adopt stable tertiary or secondary structures. While at least 40% of the human proteome is classified as IDPs, only a subset exhibit phase separation behavior. Previous work created a computer algorithm called ParSe (partition sequence) that successfully predicts folded, ID, and phase-separating (PS) IDRs from the protein primary sequence. This algorithm uses the polymer scaling exponent, v, and a conformational parameter, the intrinsic beta-turn propensity, to distinguish the three protein classes (folded, F; disordered, D; and phase-separating disordered, P). Here, we confirm that the v and beta-turn propensity values follow a normal distribution in three expanded protein sequence sets (PS-IDR, IDR, and Folded). Next, we determined the ability of 568 intrinsic sequence-based properties to define the F, D, and P populations in the sequence sets. We found that most of these properties yield statistically significant differences in the means of the sequence sets. Principal component analysis identified two principal modes of variance in the human proteome: one corresponding to physiochemical properties, like hydrophobicity, charge, or v, and the other to conformational propensities, like preferences for alpha-helix, beta-turn, or beta-sheet. These results established that a hydrophobicity scale could accurately distinguish between folded and ID populations, and that an alpha-helix scale paired with v could optimally identify PS-IDR from IDR. Using those three parameters, a second-generation version of ParSe was developed.
dc.description.departmentChemistry and Biochemistry
dc.formatText
dc.format.extent83 pages
dc.format.medium1 file (.pdf)
dc.identifier.citationIbrahim, A. (2022). Sequence-based properties that identify intrinsically disordered phase-separating protein regions (Unpublished thesis). Texas State University, San Marcos, Texas.
dc.identifier.urihttps://hdl.handle.net/10877/16119
dc.language.isoen
dc.subjectintrinsically disordered proteins
dc.subjectliquid-liquid phase separation
dc.titleSequence-Based Properties that Identify Intrinsically Disordered Phase-Separating Protein Regions
dc.typeThesis
thesis.degree.departmentChemistry and Biochemistry
thesis.degree.disciplineBiochemistry
thesis.degree.grantorTexas State University
thesis.degree.levelMasters
thesis.degree.nameMaster of Science

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