Single-molecule studies of the conformational dynamics of ABC proteins

Marijn de Boer

Research output: ThesisThesis fully internal (DIV)

301 Downloads (Pure)

Abstract

ATP-binding cassette (ABC) proteins are an important group of proteins that are involved in various key processes in all organisms. The working mechanism of these proteins is based on the precisely coordinated changes in their three-dimensional structure. Valuable insight into the structure and changes thereof have been obtained over the past decades. However, little is known about the dynamics as well as the existence of any heterogeneity or occurrences of rare events. To address this, methods were used and developed to study ABC proteins at the single-molecule level. These measurements revealed an unrecognized complexity in the structural changes in ABC proteins. It was shown that ABC proteins can adopt many more structural states as was initially believed. By simultaneously examining the structural changes and the binding of small molecules, direct insight into how ABC proteins switch between different structural states could be obtained. From this, we observed that structural changes in ABC proteins are not only driven by the interaction with other proteins or molecules but can also occur spontaneously. By combining the single-molecule measurements with theoretical research, we could provide new insights into how ABC proteins work. Understanding the working mechanism of ABC proteins can assist in drug development against diseases that are caused by misfunctioning of human ABC proteins, and in the development of antibiotics against pathogenic bacteria.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Groningen
Supervisors/Advisors
  • Cordes, Thorben, Supervisor
  • van der Giessen, Erik, Supervisor
  • Gkouridis, Giorgios, Co-supervisor
Award date2-Jun-2020
Place of Publication[Groningen]
Publisher
Print ISBNs978-94-034-2641-9
Electronic ISBNs978-94-034-2640-2
DOIs
Publication statusPublished - 2020

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