Biomacromolecular assemblies: from quinary interactions to diffusion in mammalian cells

Gopan, Gopika

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https://hdl.handle.net/2142/121274 Copy

Description

Title

Biomacromolecular assemblies: from quinary interactions to diffusion in mammalian cells

Author(s)

Gopan, Gopika

Issue Date

2023-07-14

Director of Research (if dissertation) or Advisor (if thesis)

Gruebele, Martin

Doctoral Committee Chair(s)

Gruebele, Martin

Committee Member(s)

• Luthey-Schulten, Zaida
• Selvin, Paul
• Vura-Weis, Josh

Department of Study

Chemistry

Discipline

Chemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Macromolecules
• quinary interactions
• protein-RNA interactions
• RNA binding domains
• macromolecular crowding phase separation
• diffusion
• MINFLUX
• viral capsid
• single-molecule tracking

Abstract

The cellular environment is highly complex, and the structure and function of macromolecules are controlled by weak interactions in the cell, that can be broadly categorized as macromolecular crowding, sticking and quinary interactions. The effect of these interactions on protein stability and dynamics have been studied extensively for the past few decades. There is a growing interest to further understand how these forces act together to fine tune the cell’s environment to regulate stability and activity of macromolecular assemblies. I begin by discussing how physiological environment affects the structure and function of biomolecules. In Chapter 1, I introduce macromolecular crowding, sticking and quinary interactions that act upon biomolecules in the cell. I provide a brief overview and summarize several studies in the past that have demonstrated the impact of these weak interactions and highlight the importance for a deeper understanding in the field. In Chapter 2, I focus on the role of unconventional RNA binding domains in stabilizing protein-RNA interactions and highlight the need to look beyond the conventionally identified globular binding domains. I study an extended RNA binding domain on the spliceosomal protein U1-70K and quantify the thermodynamics and kinetics of RNA binding. In Chapter 3, I discuss the subcellular localization and distribution of U1-70K to understand the role of it’s intrinsically disordered regions and RNA binding domains in navigating the membrane-bound and membrane-less compartments in the cell in order to perform it’s function. Finally, Chapter 4 describes the efforts to understand the effect of macromolecular crowding on protein diffusion. I use Hepatitis B viral capsid as a model system to study how the diffusion in the cytoplasm of human liver cells varies under different crowding conditions achieved through cell volume modulation.

Graduation Semester

2023-08

Type of Resource

Thesis

Copyright and License Information

Copyright 2023 Gopika Gopan

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