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The effect of lipids on protein structure and function

Schumann-Gillett, Alexandra

Description

Lipids and proteins are integral to all organisms' cellular structure and function. These molecules not only physically encase the contents of the cell; they also interact with each other to serve functional roles, such as signalling. As protein science has become an established field, the scientific community is becoming increasingly aware of the multi-faceted roles that lipids play in cells, and the implications of their interactions with proteins. Molecular dynamics simulation techniques are...[Show more]

dc.contributor.authorSchumann-Gillett, Alexandra
dc.date.accessioned2019-05-25T00:57:10Z
dc.date.available2019-05-25T00:57:10Z
dc.identifier.otherb59286659
dc.identifier.urihttp://hdl.handle.net/1885/163687
dc.description.abstractLipids and proteins are integral to all organisms' cellular structure and function. These molecules not only physically encase the contents of the cell; they also interact with each other to serve functional roles, such as signalling. As protein science has become an established field, the scientific community is becoming increasingly aware of the multi-faceted roles that lipids play in cells, and the implications of their interactions with proteins. Molecular dynamics simulation techniques are ideal tools to use to study these processes, as they allow the user to tease apart the molecular interactions in atomic detail and at picosecond to microsecond timescales-spatial and temporal scales that are largely inaccessible to experiments. Here, I used molecular dynamics simulation techniques to understand how lipids affect biological systems. I have studied the following: oxidised phospholipids in bilayers; bioactive lipids and the membrane protein, GlyT2; the lipid PI3P and the protein, collybistin; and phospholipids and drug transport in the multidrug transport protein, P-glycoprotein (P-gp). Firstly, I found that relatively small concentrations of oxidised phospholipids can alter the biophysical properties of a bilayer, and cholesterol can modulate these effects. Second, so-called "bioactive" lipids can alter the function of the neurotransmitter transporter protein, GlyT2, without altering the properties of the surrounding membrane. I also identified an allosteric binding site for these lipids on GlyT2. Third, a mutation in the GDP-GTP exchange factor, collybistin, influences the conformations and shape of the binding site for the phosphoinositide PI3P. Finally, I found that the ABC transporter, P-gp, has binding sites for chemically diverse compounds in its membrane-embedded domains. Overall, this thesis presents novel insights into how different lipids behave in cellular environments, whether that is within a membrane or when interacting with distinct proteins. My work highlights the structural and functional roles that lipids play in biology, which are still gaining research popularity and largely remain to be explored, and reinforces the necessity of studying biological lipids.
dc.language.isoen_AU
dc.titleThe effect of lipids on protein structure and function
dc.typeThesis (PhD)
local.contributor.supervisorO'Mara, Megan
local.contributor.supervisorcontactu4022190@anu.edu.au
dc.date.issued2019
local.identifier.doi10.25911/5d51485e2be75
local.identifier.proquestNo
local.thesisANUonly.authord61ea73b-3143-4bc7-98d0-39f31ebf0fa3
local.thesisANUonly.title000000000011_TC_1
local.thesisANUonly.keyada003d3-3a6a-d55f-4ee0-16f92dfaf069
local.mintdoimint
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